Interstitial Lung Disease Patients Research Articles

Prevalence and clinical features of interstitial lung disease in patients with psoriasis

BackgroundDespite the autoimmune nature of psoriasis, the potential association between psoriasis and interstitial lung disease (ILD) remains underexplored. This study aimed to investigate the frequency and clinical features of ILD in patients with psoriasis and propose a new conceptual framework of “ILD associated with psoriasis”.MethodsA retrospective analysis of 117 patients with psoriasis was conducted, excluding those without chest imaging prior to methotrexate or biologic use and those with other comorbidities leading to ILD.ResultsILD was identified in 12 (10%) patients with psoriasis; 6/50 with psoriasis vulgaris and 6/65 with psoriatic arthritis. Three of 12 patients had no history of smoking. Serum Krebs von den Lungen-6 (KL-6) levels were elevated in patients with ILD compared to those in patients without ILD. The indeterminate for usual interstitial pneumonia (UIP) pattern was the most prevalent CT finding. A lung biopsy specimen from a representative case revealed equivalent indeterminate for UIP. Over a median 8.9-year observation period, ILD progressed in only 5 patients, with no cases of respiratory failure or death due to ILD progression, suggesting generally favourable prognoses.ConclusionsILD associated with psoriasis would be present, and its frequency is 10% of patients with psoriasis. We propose that chest radiography and a serum KL-6 test at the initial diagnosis of psoriasis would be useful in screening for the detection of ILD. We also recommend that a physician diagnosing ILD should carefully examine the skin findings, considering if psoriasis could be associated with ILD.Trial registrationNot applicable.

Clinical features, radiological findings and prognosis of microscopic polyangiitis with interstitial lung disease: a retrospective matched control study

BackgroundThe association between interstitial lung disease (ILD) and microscopic polyangiitis (MPA) has received increasing attention in recent years. However, there are still no studies comparing clinical characteristics and prognoses between MPA-ILD patients and patients with ANCA-negative ILDs. Therefore, the purpose of this study was to analyse a group of patients presenting MPA-ILD matched with patients exhibiting ANCA-negative ILDs to identify differences in their clinical characteristics and survival.MethodsThis study retrospectively reviewed the data of 60 patients with MPA-ILD and 60 patients with ANCA-negative ILDs who were matched for age, sex, and patterns on chest high-resolution CT (HRCT) images. The baseline clinical information, laboratory parameters and chest CT data were collected and analysed at each patient’s initial diagnosis.ResultsSixty of the 682 (8.8%) ILD patients were diagnosed with MPA-ILD. MPA-ILD patients tended to be older and have higher CRP and ESR levels. ILD antedated MPA in 61.7% (37/60) of the patients, and MPA occurred on average (45.1 ± 33.4) months after the ILD diagnosis. Compared with matched ANCA-negative ILD patients, MPA-ILD patients had higher CRP and serum creatinine levels and lower haemoglobin levels. UIP (63.3%) was the most common chest HRCT pattern, and the proportion of patients with oddly shaped cysts (P = 0.04) was significantly greater in the MPA-ILD group than in the matched ANCA-negative ILD group. The number of MPA-ILD patients was significantly shorter than that of ANCA-negative ILD patients (P = 0.005). Survival analysis revealed that acute exacerbation (AE) of ILD (HR 2.40, 95% CI 1.03–5.59, P = 0.043) and diffuse alveolar haemorrhage (HR 3.42, 95% CI 1.09–10.73, P = 0.036) were independently associated with shorter survival and that receiving glucocorticoids combined with immunosuppressants (HR 0.11, 95% CI 0.03–0.37, P < 0.001) was independently associated with prolonged survival in MPA-ILD patients.ConclusionsThe proportion of MPA-ILD patients with total ILD is not low, and ANCA testing of ILD patients is necessary. Oddly shaped cysts with a UIP pattern may be a characteristic chest imaging manifestation of MPA-ILD. The prognosis of MPA-ILD is poor, especially for patients who are older, have DAH, and have experienced AEs.

Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis – a nested case-control study within the German biologics register RABBIT

BackgroundTo investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).MethodsWe analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months.ResultsWe identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings.ConclusionHigher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.

Nintedanib and its combination with immunosuppressives in connective tissue disease-related interstitial lung diseases.

Nintedanib reduces the decline of pulmonary function in patients with advancing lung fibrosis. To assess the characteristics of the patients with connective tissue diseases (CTDs) related to interstitial lung disease (ILD) under nintedanib treatment. The CTD-related ILD patients under nintedanib treatment who were followed up between 2020 and 2023 were included in the study. The clinical data of the patients before and after nintedanib were evaluated retrospectively. There were 36 patients (19 female) with a mean age of 65.2 ± 8.5 years who were treated with nintedanib. The median duration for nintedanib treatment was 19 months. The most common CTD was Sjogren's syndrome (36.1%), followed by systemic sclerosis (27.8%), rheumatoid arthritis (25%), undifferentiated CTD (8.3%), and inflammatory myositis (2.8%). Fifteen (41.7%) patients had impaired pulmonary function tests (FVC < 70 ml and/or DLco < 80 ml), and 23 (63.9%) patients had ≥ 20% involvement of parenchyma in high-resolution computed tomography (HRCT) before nintedanib. According to HRCT findings, 25 (69.4%) patients had the usual interstitial pneumonia pattern. All patients had 300 mg/day of nintedanib and received at least one immunosuppressive treatment during the study period. The mean %predicted value of FVC was 82.8 ± 17.6, and DLco was 65.3 ± 19.2 before nintedanib treatment. Following the 6-month follow-up, FVC showed an increase to 92.3 ± 15.8 (with an R correlation coefficient of 0.54, p = 0.025), and 22 (61.1%) patients exhibited either stabilization or regression of findings on HRCT. Nintedanib emerges as a promising therapeutic agent compatible with immunosuppressives for treating progressive lung fibrosis in patients with CTD-related ILD.

Clinical features and risk factors of invasive pulmonary aspergillosis in interstitial lung disease patients

BackgroundThe prevalence of invasive pulmonary aspergillosis (IPA) among patients with interstitial lung disease (ILD) is steadily increasing, leading to high mortality. The purpose of this study is to analyze the clinical features and risk factors of IPA in patients with ILD.Methods353 hospitalized ILD patients admitted in Nanjing Drum Tower Hospital from March 2023 and April 2024 were enrolled. The enrolled patients were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups.ResultsAmong 353 patients with ILD, 58 who suffered from IPA were identified. Among them, 2 (3.4%) episodes of proven IPA and 56 (96.6%) of probable IPA were diagnosed. The median age was 68.4 ± 8.6 years, and 35 patients were men. The forms of ILD included idiopathic pulmonary fibrosis (n = 21), interstitial pneumonia with autoimmune features (n = 13), rheumatoid arthritis related interstitial pneumonia (n = 11) and Sjögren′s syndrome (n = 4). The clinical features of IPA in ILD were cough (100.0%), dyspnea (93.1%) and fever (55.2%). Chest CT images showed reticulation (87.9%), traction bronchiectasis (84.5%), GGO (77.6%), honeycombing (69.0%), consolidation (44.8%) and pleural effusion (24.1%). The incidence of honeycombing and consolidation were higher in ILD patients with IPA compared to control group (P < 0.05). The main pathogens were A. fumigatus (50.0%) and A. flavus (29.3%). Following the diagnosis of IPA, all patients were treated with antifungal drugs. The overall survival rate after 90 days was 74.1%. Multivariate conditional Logistic regression analysis showed that lymphopenia (OR = 2.745, 95% CI 1.344–5.607) and honeycombing (OR = 2.915, 95% CI 1.429–5.949) were the risk factors of ILD with IPA (P < 0.05).ConclusionIPA is one of the major complications of ILD and its prognosis is poor. Lymphopenia and honeycombing increased the risk of IPA in ILD patients.

Development of a machine learning model in prediction of the rapid progression of interstitial lung disease in patients with idiopathic inflammatory myopathy.

Rapidly progressive interstitial lung disease (RP-ILD) significantly impacts the prognosis of patients with idiopathic inflammatory myopathies (IIM). High-resolution computed tomography (HRCT) is a crucial noninvasive technique for evaluating interstitial lung disease (ILD). Utilizing quantitative computed tomography (QCT) enables accurate quantification of disease severity and evaluation of prognosis, thereby serving as a crucial computer-aided diagnostic method. This study aimed to establish and validate a machine learning (ML) model to predict RP-ILD in patients with idiopathic inflammatory myopathy-related interstitial lung disease (IIM-ILD) based on QCT and clinical features. A total of 514 patients (367 females, median age 54 years) with IIM-ILD in the China-Japan Friendship Hospital were retrospectively included, out of which 249 cases (165 females, median age 55 years) were identified as having RP-ILD. To extract the quantitative features on HRCT, deep learning (DL) methods were employed, along with demographic factors, pulmonary function test results, and blood gas analysis results; these factors were integrated into a final prediction model. Logistic regression was chosen as the final model due to its superior area under the curve (AUC) and explainability compared to the other seven ML models. The validation dataset yielded an AUC of 0.882 [95% confidence interval (CI): 0.797-0.967], indicating that the combined QCT and clinical features model outperformed both the QCT-only model and the clinically-only model. In calibration and clinical decision curve analysis, the final model demonstrated minimal prediction bias (concordance index: 0.887, 95% CI: 0.800-0.974, P<0.001) and provided greater net benefit across most thresholds. The nomogram encompassed the incorporation of the following variables: subtype, gender, forced expiratory volume in one second (FEV1%), diffusing capacity for carbon monoxide (DLCO%), oxygenation index (OI), and quantitative ground-glass opacities (GGOs), consolidation, pulmonary vascular, and branches on HRCT. When utilizing ML techniques, the baseline QCT has the potential to predict rapid progression in patients with IIM-ILD. The prediction performance will be further improved by incorporating clinical data alongside HRCT features. Idiopathic inflammatory myopathy (IIM); rapidly progressive interstitial lung disease (RP-ILD); high-resolution computed tomography (HRCT); machine learning (ML); quantitative computed tomography (QCT).

Hypersensitivity Pneumonitis Radiologic Features in Interstitial Lung Diseases

The radiologic criteria of hypersensitivity pneumonitis (HP) guidelines focus on four HP compatible features (HPCF) in high-resolution computed tomography (HRCT): ground glass opacities, mosaic attenuation, air-trapping, and centrilobular nodules. However, evidence to support these criteria are limited. Consecutive interstitial lung disease (ILD) patients who underwent HRCT between 2016 and 2021 in three medical centers were included. We assessed the prevalence of HPCF in each ILD and their association with HP diagnosis. We evaluated the impact of HPCF amount for HP diagnosis and the performance of the radiologic criteria by the ATS/JRS/ALAT and CHEST HP guidelines. 436 patients with ILD were included (mean age 66, 48% females), of them, 56 (13%) with HP. All four HPCF were more prevalent in HP than in non-HP ILD (p<0.001 for all). In multivariate analysis, air-trapping was the strongest independent predictor (AOR 4.1, 95% CI 2-8.4, p<0.001). Centrilobular nodules were present almost exclusively in HP and smoking-related ILD. The amount of HPCF in HRCT had an excellent predictive ability for HP diagnosis (receiver operating characteristic AUC 0.85, 95% CI 0.80-0.90). The radiologic criteria of both guidelines had high specificity for "typical HP" and high sensitivity for "compatible with HP", although with low positive predictive values. Our findings remained robust even when including only patients that had a diagnostic biopsy. The presence and amount of HPCF in HRCT predicted HP diagnosis in real-life settings. While current HP radiologic criteria demonstrated good diagnostic performance, our findings highlight areas for future improvement.

FREQUENCY OF PULMONARY HYPERTENSION IN CASES OF INTERSTITIAL LUNG DISEASE: CROSS-SECTIONAL STUDY

Pulmonary hypertension (PH) is a significant complication of interstitial lung disease (ILD), often contributing to increased morbidity and mortality. Understanding the prevalence and associated risk factors of PH in ILD patients can aid in early detection and tailored management strategies. Objective: .To determine the frequency of pulmonary hypertension in patients with interstitial lung disease. Methods: A cross-sectional study was conducted on 200 patients diagnosed with ILD. Data on demographics, clinical characteristics, smoking history, and comorbidities were collected. Pulmonary hypertension was screened using transthoracic echocardiography, defined as a mean pulmonary artery pressure (mPAP) ≥ 20 mmHg. Statistical analyses were performed to assess associations between PH and patient characteristics. Results: Pulmonary hypertension was observed in 23.5% of the study population. The mean age of participants was 50.63 ± 12.03 years, with a male predominance (56%). Smoking was significantly associated with PH (p = 0.01), with 44.7% of smokers exhibiting PH. Hypertension was common (59.0%) but showed no significant association with PH. No significant differences in PH prevalence were observed based on place of residence or employment status. Conclusion: Pulmonary hypertension is a prevalent complication in ILD, particularly among smokers and males. Routine screening for PH in ILD patients, especially those with known risk factors, is essential for early diagnosis and intervention. These findings emphasize the need for targeted management strategies to mitigate the impact of PH on this vulnerable population.

Diagnostic performance of specific biomarkers for interstitial lung disease: a single center study.

This study aimed to determine the clinical significance of Krebs von den Lungen-6 (KL-6), surfactant proteins A (SP-A) and D (SP-D) in the evaluation and management of interstitial lung disease (ILD). Serum KL-6, SP-A, SP-D levels were measured in122 unique consecutive patients referred for connective tissue disease (CTD) associated ILD (CTD-ILD) autoantibodies and 120"healthy" controls. Patients' charts were retrospectively reviewed and categorized as ILD and non-ILD or CTD-ILD and other ILD. All biomarkers were evaluated for diagnosis and moderate vs. severe ILD based on high-resolution computed tomography (HRCT). ILD was diagnosed in 52 % (n=64) and non-ILD in 48 % (n=58). ILD patients were categorized as other ILD (61 %, n=39) or CTD-ILD (39 %, n=25). Patients with ILD had significantly elevated levels of SP-A (p<0.02), KL-6 or SP-D (both p<0.0001) when compared to those with non-ILD. The mean levels of all biomarkers were significantly elevated levels in the ILD compared to non-ILD group (p<0.0001). No significant difference in biomarker levels between CTD-ILD and other ILD groups (p≥0.900). Biomarkers had comparable specificities (89-93 %) however; sensitivities were variable at 75 , 77 and 17 % for KL-6, SP-D and SP-A, respectively. Combination of KL-6 and SP-D yielded comparable diagnostic accuracy to all biomarkers with median levels significantly higher in patients with severe vs. mild disease. KL-6 and SP-D levels are elevated in ILD and therefore contribute to the diagnosis and risk stratification for patient management.

Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1

BackgroundFicolins were originally identified as proteins that bind to transforming growth factor-β1 (TGF-β1). They are capable of activating the complement system through lectin pathway for immune system protection. Ficolin-2 and 3 have been identified in patients with interstitial lung diseases (ILD) and their function in these diseases is currently being explored. In contrast, the functional role of ficolin-1 in pulmonary fibrosis is still elusive and remains to be elucidated.MethodsThe expression of ficolin-1 in the plasma of idiopathic pulmonary fibrosis (IPF) and connective tissue disease (CTD)-ILD patients was first determined. As the orthologue of human ficolin-1, ficolin-B knockout and ficolin-B overexpression were used to establish bleomycin (BLM)-induced pulmonary fibrosis mouse model. Co-immunoprecipitation, immunofluorescence and RNA sequencing were utilized to explore and expound on the expression and the functional mechanism of ficolin-1 in pulmonary fibrosis.ResultsCompared with healthy controls, plasma ficolin-1 was significantly decreased in patients with IPF and CTD-ILD. In the bleomycin (BLM)-induced mice model, ficolin-B deficiency aggravated lung injury and fibrosis. There was also observed increase in TGF-β1 levels and enhanced downstream signaling. However, the overexpression of ficolin-B showed preventative and therapeutic efficacy against lung fibrosis. Furthermore, coimmunoprecipitation studies revealed the direct interaction between ficolin-1 and TGF-β1 in human plasma, which was further confirmed by the colocalization of ficolin-1 and TGF-β1 in lung tissues.ConclusionsFicolin-1 inhibits pulmonary fibrosis by directly binding to the key profibrogenic factor TGF-β1, marking it as a potential target for therapy in the treatment of fibrotic lung diseases.

Modeling ventilation of patients with interstitial lung disease at rest and exercise: a bench study

BackgroundThe ventilatory physiopathology of patients with interstitial lung disease (ILD) remains poorly understood. We aimed to personalize a mechanical simulator to model healthy and ILD profiles ventilation, and to evaluate the effect of spontaneous breathing on respiratory mechanics at rest and during exercise.MethodsIn a 2-compartment lung simulator (ASL 5000®), we modeled 1 healthy and 3 ILD profiles, at rest and during exercise, based on physiological data from literature and patients. Measurements were: tidal volume, end-expiratory lung volume, driving pressure, transpulmonary driving pressure, dynamic alveolar strain, mechanical power, and time lag of inspiratory flow between compartments 1 and 2.ResultsHealthy and ILD models were validated: maximum differences between real and simulated tidal volume were 5% (96 ml) and 6% (54 ml) at rest and during exercise respectively, considered clinically negligible. When we simulated lung inhomogeneity (compliance in compartment 1 > compartment 2), tidal volume, end-expiratory lung volume, driving pressure and mechanical power increased in compartment 1 and decreased in compartment 2. Driving transpulmonary pressure and dynamic alveolar strain increased in compartment 2 and decreased in compartment 1. Time lag of inspiratory flow between compartments 1 and 2 was positively correlated with a difference of compliance between compartments (r = 0.98, CI95% (0.9106; 0.9962), p < 0.0001).ConclusionIn this bench study, we personalized a mechanical simulator thatmodels the lung inhomogeneity and spontaneous breathing of healthy subjects and ILD patients at rest and during exercise. Our results suggest that lung inhomogeneity could increase lung vulnerability to volo-atelec-trauma mechanisms in ILD. Further physiological studies are needed to evaluate the impact of this vulnerability on acute or chronic ILD worsening.

The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review.

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient's overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies.

Risk factors for incidence of interstitial lung disease in patients with rheumatoid arthritis: a systematic review and meta-analysis

ObjectivesThis study aimed at identifying risk factors for the incidence of interstitial lung disease in patients with rheumatoid arthritis (RA-ILD) by a systematic review and meta-analysis.MethodsInformation sources: studies published by...

Pleural Irregularities: A new ultrasound marker for lung involvement in primary Sjögren's disease

ObjectivesLung ultrasound (LUS) has been proposed as a useful tool for the assessment of interstitial lung disease (ILD) in connective tissue diseases. However, there are no studies investigating the significance of pleural irregularities (PI) on LUS in primary Sjögren's disease (SjD) patients. The aim of this study was to explore the role of PI for the assessment of SjD-related lung involvement. MethodsAll primary SjD patients who had undergone a chest CT-scan in the lasts 2 months from the start of the study were enrolled, including both SjD patients with known ILD and SjD patients without known lung involvement who underwent a chest CT due to clinical indications other than ILD screening. LUS was performed for all patients and PI total and partial scores were assigned from 0 (normal) to 2 (major changes). Based on CT-scans results SjD patients were divided into 5 groups: normal CT-scan, non SjD-related lung abnormalities, SjD-related non-ILD lung abnormalities, established ILD, newly diagnosed ILD. ResultsNineteen SjD patients with established ILD and 42 without known lung involvement who had undergone a CT-scan were included. Among the latter, CT allowed the diagnosis of 4 new ILD cases. Both total and postero-inferior PI scores were comparable between established ILD and newly diagnosed ILD patients and significantly higher compared to patients with normal CT-scan and SjD related non-ILD lung abnormalities. The AUC for ILD diagnosis was significantly higher for the PI postero-inferior score compared to the PI total score. A cut-off score of 15 for the PI postero-inferior score resulted in a sensitivity of 86.6% and specificity of 84.2% for SjD-ILD diagnosis. Both PI total and postero-inferior scores strongly correlated with HRCT Warrick score (r=0.809 and r=0.854). The correlation between PFT and both total and postero-inferior PI scores was higher than that observed between PFT and the Warrick HRCT score. ConclusionsPI may represent a valid tool for the assessment of lung involvement in SjD, particularly for the screening of ILD. PI limited to postero-inferior lung fields seem to maintain good diagnostic accuracy, allowing to save time in clinical practice.

Admission chest CT scan of intensive care patients with interstitial lung disease: Unveiling its limited predictive value through visual and automated analyses in a retrospective study (ILDICTO)

BackgroundClinical course prediction of patients with interstitial lung disease (ILD) admitted to the intensive care unit (ICU) for acute respiratory failure (ARF) can be challenging. This study aimed to characterize the prognostic value of admission chest CT-scan in this situation. MethodsWe retrospectively included ILD patients admitted to a French ICU for acute respiratory failure requiring oxygen. Patients with lymphangitis carcinomatosis and ANCA vasculitis were excluded. We analyzed every admission chest CT-scan using two different approaches: a visual analysis (grading the extent of traction bronchiectasis, ground glass and honeycomb) and an automated analysis (grading the extent of ground glass and consolidation with a dedicated software). The primary outcome was ICU mortality. ResultsBetween January 2014 and October 2020, 81 patients presented an acute respiratory failure with ILD on the admission chest CT-scan. In univariate analysis, only the main pulmonary artery diameter differed between patients who survived and those who died in ICU (30 vs 32 mm, p = 0.021). In multivariate analysis, none of the radiological funding was associated with ICU mortality. Visual and automated analyses did not yield different results, with a strong correlation between the two methods. However, the identification of an UIP pattern (and the presence of honeycomb) was associated with a poorer response to corticosteroid therapy. ConclusionOur study showed that the extent of radiological findings and the severity of fibrosis indices on admission chest CT scans of ILD patients admitted to the ICU for ARF were not associated with subsequent deterioration.

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.

Long-term outcome of interstitial lung disease in patients with primary Sjögren's syndrome: a retrospective observational study.

Interstitial lung disease (ILD) is a potentially serious but underdiagnosed manifestation of primary Sjögren's syndrome (pSS). This observational study investigated the prevalence and clinical course of ILD in pSS, together with prognostic factors. A multicenter, retrospective longitudinal study was performed using findings from baseline and follow-up pulmonary function tests and chest computed tomography. Predisposing factors for the development of ILD and acute exacerbation (AE) were identified using a logistic regression model. The risk factors for a significant decline of pulmonary function were determined by the Cox proportional hazard model. A total of 1,306 patients with pSS were included in this study (female, 98%; mean age, 54 years). Among them, 79 patients with pSS were comorbid with ILD. ILD was more frequently found in male, older patients. Nonspecific interstitial pneumonia was the most prevalent imaging pattern in pSS-ILD (51%), followed by usual interstitial pneumonia (22%). At diagnosis with pSS-ILD, 54% of patients had restrictive pulmonary function, and 41% of patients initiated pharmacological treatment. During the median 4-year follow-up period, AE, a significant decline in pulmonary function, and death occurred in 19%, 29%, and 9% of patients with pSS-ILD, respectively. The neutrophil-to-lymphocyte ratio (NLR) increased 3 months prior to AE, and it was associated with AE. Older age at pSS-ILD diagnosis was a prognostic factor for a significant decline in pulmonary function. ILD accounted for 6% of the comorbidity of pSS. AE was associated with a significant decline in pulmonary function, and the NLR may predict AE.

Quantification of autoantibodies using a luminescent profiling method in autoimmune interstitial lung disease.

Autoantibodies are important for the diagnosis of autoimmune interstitial lung disease (ILD). Standard immunoassays have limitations, including their qualitative nature and/or a narrow dynamic range of detection, hindering the usefulness of autoantibodies as biomarkers of disease activity. Here, the luciferase immunoprecipitation system (LIPS) was evaluated for measuring myositis-specific and other lung-related autoantibodies in 25 subjects with idiopathic inflammatory myopathies (IIM), 26 with Sjögren's disease (SjD), and 10 healthy volunteers. LIPS detected a broad dynamic range of autoantibodies, to MDA5, Jo-1, PL12, KS, U1-70K, and Ro52, and matched seropositivity status with established immunoassays. Robust anti-MDA5 autoantibodies in four IIM-ILD patients had a median value of 1,134,000 LU (IQR 473,000-2,317,000), which was 500 times higher than in 21 seronegative IIM patients. Markedly elevated anti-Jo-1 autoantibodies in five IIM-ILD patients demonstrated a median value of 1,177,000 LU (IQR: 604,000-2,520,000), which was 1000-fold higher than in seronegative patients. Robust anti-Ro52 and other anti-tRNA-synthetase autoantibodies were detected in a subset of IIM-ILD subjects. In SjD, only anti-U1-70K and KS autoantibodies were identified in ILD patients with a prevalence of 30% and 20%, respectively. In longitudinal samples of five IIM-ILD patients, anti-Jo-1 autoantibody levels paralleled clinical improvement of lung function. LIPS can accurately quantify autoantibody levels as biomarkers for treatment response in patients with autoimmune ILD.

Correlation between CT-based phenotypes and serum biomarker in interstitial lung diseases

BackgroundThe quantitative analysis of computed tomography (CT) and Krebs von den Lungen-6 (KL-6) serum level has gained importance in the diagnosis, monitoring, and prognostication of interstitial lung disease (ILD). However, the associations between quantitative analysis of CT and serum KL-6 level remain poorly understood.MethodsIn this retrospective observational study conducted at tertiary hospital between June 2020 and March 2022, quantitative analysis of CT was performed using the deep learning-based method including reticulation, ground glass opacity (GGO), honeycombing, and consolidation. We investigated the associations between CT-based phenotypes and serum KL-6 measured within three months of the CT scan. Furthermore, we evaluated the performance of the combined CT-based phenotypes and KL-6 levels in predicting hospitalizations due to respiratory reasons of ILD patients.ResultsA total of 131 ILD patients (104 males) with a median age of 67 years were included in this study. Reticulation, GGO, honeycombing, and consolidation extents showed a positive correlation with KL-6 levels. [Reticulation, correlation coefficient (r) = 0.567, p < 0.001; GGO, r = 0.355, p < 0.001; honeycombing, r = 0.174, p = 0.046; and consolidation, r = 0.446, p < 0.001]. Additionally, the area under the ROC of the combined reticulation and KL-6 for hospitalizations due to respiratory reasons was 0.810 (p < 0.001).ConclusionsQuantitative analysis of CT features and serum KL-6 levels ascertained a positive correlation between the two. In addition, the combination of reticulation and KL-6 shows potential for predicting hospitalizations of ILD patients due to respiratory causes. The combination of reticulation, focusing on phenotypic change in lung parenchyma, and KL-6, as an indicator of lung injury extent, could be helpful for monitoring and predicting the prognosis of various types of ILD.

Myositis-Associated Interstitial Lung Disease: The Experience of a Tertiary Center.

Background: Interstitial lung disease (ILD) is a common extra-muscular manifestation of idiopathic inflammatory myopathies (IIMs), often associated with a poorer prognosis and increased mortality risk. Methods: This retrospective study aimed to characterize lung involvement and treatment response in an IIM cohort at a Portuguese tertiary center, followed between June 2016 and March 2024. We analyzed data from high-resolution computed tomography (HRCT) scans and pulmonary function tests (PFTs) to assess associations with autoantibody profiles and treatment regimens. Results: A total of 198 patients were included, with 69 (34.8%) exhibiting ILD. Antisynthetase syndrome (ASyS) and dermatomyositis were the most common diagnoses among IIM-ILD patients, with ASyS being significantly more frequent in this group than in non-ILD patients (p < 0.001). Anti-Jo1 and anti-MDA-5 antibodies were more frequent in ILD patients (p < 0.001 and p = 0.021), while anti-Mi2 antibodies were less common (p = 0.002). Non-specific interstitial pneumonia (NSIP) was the most common radiological pattern (69.5%). IIM-ILD patients presented with significantly lower forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) compared to non-ILD patients (p < 0.001 for all values). Longitudinal analysis showed improved DLCO (p = 0.022) and stable or improved FVC (p = 0.097), especially with intravenous immunoglobulin (IVIg) and azathioprine (AZA). Combination therapies including IVIg with mycophenolate mofetil (MMF) or rituximab (RTX) also improved DLCO and FVC. Most ILD patients (89.6%) had stable HRCT patterns over time. Conclusions: Our findings highlight the potential for stabilizing or even improving lung function in IIM-ILD with appropriate immunosuppressive therapy, particularly with regimens incorporating IVIg and AZA, and combination therapies.