Interstitial Lung Disease Patients Research Articles

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.

The Interstitial Lung Disease Patient Pathway: From Referral To Diagnosis

BackgroundSuspected Interstitial Lung Disease (ILD) patients may be referred to an ILD-specialist centre or non-ILD-specialist centre for diagnosis and treatment. Early referral and management of patients at ILD-specialist centres has been shown to improve survival and reduce hospitalisations. The COVID-19 pandemic has affected the ILD patient diagnostic pathway and prompted centres to adapt.AimsThis study investigates and contrasts ILD patient pathways in ILD-specialist and non-ILD-specialist centres, focusing on referrals, caseloads, diagnostic tools, multi-disciplinary team (MDT) meeting practices, and resource accessibility.MethodsConducted as a cross-sectional study, a global self-selecting survey ran from September 2022 to January 2023. Participants included ILD specialists and healthcare professionals (HCPs) from ILD-specialist centres and non-ILD-specialist centres.ResultsOf 363 unique respondents from 64 countries, 259 were from ILD-specialist centres and 104 from non-ILD-specialist centres. ILD centres had better resource availability, exhibiting higher utilisation of diagnostic tests (median: 12 tests), than non-ILD centres (9 tests); and better access to specialist professions attending MDTs (median: 6 professions at meeting) in specialist centres than non-ILD centres (3 professions at meeting). Transitioning to virtual MDTs allowed HCPs from outside of centres to join meetings in nearly 90% of all centres, increasing regular participation in 60% of specialist centres and 72% of non-ILD centres. For treatment of patients, specialist centres had better access to antifibrotic drugs (91%) compared to non-ILD centres (60%).ConclusionsDiagnostic pathways for ILD patients diverged between specialist centres and non-ILD centres. Disparities in resource and specialist availability existed between centres.

Exploring the Potential Value of [68Ga]Ga-FAPI-46 PET/CT for Molecular Assessment of Fibroblast Activation in Interstitial Lung Disease: A Single-Center Pilot Study.

The aim of the study was to evaluate the association of high-resolution computed tomography (HRCT) findings with pulmonary fibrotic activity in the corresponding regions using [68Ga]Ga-fibroblast activation fibroblast inhibitor (FAPI) PET/CT in patients with interstitial lung disease (ILD). Additionally, the potential of [68Ga]Ga-FAPI-46 PET/CT for evaluating the active fibrosis process and 99mTc-MIBI scintigraphy for assessing the inflammatory process in ILD patients was also assessed. In this pilot study, 20 ILD patients underwent [68Ga]Ga-FAPI-46 PET/CT and 99mTc-MIBI SPECT/CT. Additionally, 10 patients without lung or thoracic involvement who were undergoing [68Ga]Ga-FAPI PET/CT for cancer detection were enrolled in the control group. The images were evaluated both visually and semiquantitatively and also compared with HRCT and pulmonary function tests. Multiple quantitative parameters were derived from the lung segments in the PET scan, including SUVmax, SUVmean, maximum target-to-liver ratio, mean target-to-liver ratio (TLRmean), and total lesion FAPI expression for the entire lung, as well as its lobes and zones. Additionally, the maximum Hounsfield unit (HU) and mean HU in HRCT were calculated for the whole lung as well as its lobes and zones. Furthermore, an HRCT fibrosis score (HFS) was defined according to the HRCT findings. Twenty ILD patients with a mean age of 58.70 (SD, 11.09) years were enrolled. Additionally, 10 control patients were enrolled with a mean age of 57.70 (SD, 15.19) years. Based on visual assessment, the FAPI scan was positive in 12 (60%) patients. Similarly, the MIBI scan was positive in 12 (60%) patients. In the 20 ILD cases, both scans were positive in 6 cases, and both were negative in 2 cases. Six cases showed FAPI-negative and MIBI-positive results, whereas another 6 cases showed FAPI-positive and MIBI-negative results. Comparing the control and ILD patients, there was a significant difference in SUVmax, SUVmean, total lesion FAPI expression, TLRmean, maximum HU, and mean HU (P < 0.05). When comparing HFS with PET-derived parameters in zones, a significant positive correlation was found between HFS and SUVmean, SUVmax, maximum target-to-liver ratio, and TLRmean (P < 0.05). Additionally, a significant difference was noted between FAPI results and HFS (P = 0.003). An ancillary finding, 9 of 20 (45%) ILD patients showed intense FAPI uptakes in gallbladder, whereas none of the 10 in the control group showed such uptake. The present study may suggest that combining [68Ga]Ga-FAPI PET/CT and 99mTc-MIBI SPECT/CT yields an additive effect for evaluating ILD-related fibrosis and inflammatory processes over using either modality alone. Furthermore, it appears that [68Ga]Ga-FAPI PET/CT has the potential to ascertain levels of fibrotic activity from population of resident fibroblasts, active fibroblasts, and scar maturation among ILD patients based on their HRCT patterns.

Microplastics, as a risk factor in the development of interstitial lung disease- a preliminary study

Microplastic (MPs) pollution is a global concern that affects all living organisms, yet research on MP-related disorders in humans, including incidence and symptoms, remains limited. In this study, the presence, composition, and characterization of MPs in bronchoalveolar lavage (BAL), which reflects lung tissue, and blood were examined. Fiberoptic bronchoscopy was performed to collect BAL samples from patients suspected of having interstitial lung disease (ILD) as well as from a control group. MPs were identified and measured using μ-Raman techniques.In BAL samples, the most common MPs color observed was grey/white, with sizes ranging from 4.19 to 792.00 μm. The particle shapes and polymer types identified included polyamide (PA), polyester (PET), polyvinyl chloride (PVC), and polyurethanes (PU). For blood samples, MPs were predominantly grey/white and blue, with sizes ranging from 13.14 to 20. 29 μm. The identified polymers in blood samples included polyamide (PA) and polyethylene (PE). MPs were detected in 10 out of 18 patients (55%) suspected of having ILD, with most of these patients presenting with the fibrotic type of the disease. In the control group, two patients whose BAL samples were positive for MPs were found to have chronic lung disease.This study is the first to explore the relationship between interstitial lung disease (ILD) and microplastics (MPs), revealing a tendency for the presence of MPs in the bronchoalveolar lavage (BAL) of ILD patients, particularly those with a fibrotic phenotype. Further research is needed to determine the cumulative effects of MPs on human health, especially concerning the respiratory system, which is highly exposed to environmental pollutants.

Clinical utility of lung ultrasound for the detection of interstitial lung disease in patients with rheumatoid arthritis.

To establish the diagnostic value of lung ultrasound (LUS) in patients with rheumatoid arthritis (RA) for the detection of interstitial lung disease (ILD). A cross-sectional study was performed. Consecutive patients with RA (American College of Rheumatology/European League Against Rheumatism 2010 criteria) who had a chest high-resolution computed tomography (HRCT) performed within 12 months before inclusion, regardless of symptomatology, were included. Demographic, clinical, laboratory, and pharmacological data were recorded. Each patient underwent a LUS with assessment of B-lines (BL) and pleural irregularities (PI). HRCT was considered the gold standard for the confirmatory diagnosis of ILD. Receiver operating characteristic (ROC) curves were calculated to test the ability of LUS findings (BL and PI) in discriminating patients with ILD. A total of 104 RA patients were included, of which 21.8% had ILD. Patients with ILD had more BL (median 26 versus 1, p<0.001) and PI (median 16 versus 5, p<0.001) than patients without ILD. The diagnostic accuracy in ROC curves was: area under the curve (AUC) 0.88 and 95% confidence interval (CI) 0.78-0.93 for BL and AUC 0.82 and 95% CI 0.74-0.89 for PI. The best cut-off points for (ILD detection) discriminating the presence of significant interstitial lung abnormalities were 8 BL and 7 PI. The presence of 8 BL and/or 7 PI in the LUS showed an adequate cut-off value for discriminating the presence of significant interstitial lung abnormalities, evocative of ILD.

Noninvasive diagnostic modalities and prediction models for detecting pulmonary hypertension associated with interstitial lung disease: a narrative review.

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH 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.

Discrepancy between pulmonary arterial wedge pressure and left ventricular end diastolic pressure in patients with interstitial lung disease

BackgroundRight heart catheterization (RHC) is the gold standard for diagnosing pulmonary hypertension (PH) in patients with interstitial lung disease (ILD). However, discrepancies between pulmonary arterial wedge pressure (PAWP) and left ventricular end-diastolic pressure (LVEDP) remain understudied in this population. MethodsWe conducted a retrospective analysis of data from ILD patients who underwent RHC and had concomitant LVEDP measurements. Pulmonary vascular resistance (PVR) was calculated using both PAWP and LVEDP. Patients were categorized based on PAWP and LVEDP values using a threshold of 15 mmHg and PVR values using a threshold of 2 or 3 Wood Units. After that patients were categorized as concordant or discordant if both values were on the same or opposite sides of these thresholds, respectively. A discordantly higher PAWP group (left atrial dysfunction, LAD) was defined as patients with a PAWP-LVEDP difference of more than 3mmHg. ResultsAmong 87 ILD patients, 9 patients (10.3%) showed discordance between PAWP and LVEDP. LAD was observed in 12 patients (13.8%) and was associated with lower forced vital capacity (Odd ratio [OR]: 0.956, p = 0.049) and a larger left atrium diameter (OR: 3.205, p = 0.033). Discordance in PVR values was also noted, with potential treatment targets for PH-specific therapy differing in 9 patients (22.0%) depending on whether PAWP or LVEDP was used. ConclusionsThis study highlights the clinical significance of PAWP-LVEDP discrepancies in suspected PH-ILD patients, emphasizing the need for comprehensive assessments incorporating LVEDP and clinical context for accurate diagnosis, risk stratification, and treatment decisions.

Novel prediction model of early screening lung adenocarcinoma with pulmonary fibrosis based on haematological index

BackgroundLung cancer (LC), a paramount global life-threatening condition causing significant mortality, is most commonly characterized by its subtype, lung adenocarcinoma (LUAD). Concomitant with LC, pulmonary fibrosis (PF) and interstitial lung disease (ILD) contribute to an intricate landscape of respiratory diseases. Idiopathic pulmonary fibrosis (IPF) in association with LC has been explored. However, other fibrotic interrelations remain underrepresented, especially for LUAD-PF and LUAD-ILD.MethodsWe analysed data with statistical analysis from 7,137 healthy individuals, 7,762 LUAD patients, 7,955 ILD patients, and 2,124 complex PF patients collected over ten years. Furthermore, to identify blood indicators related to lung disease and its complications and compare the relationships between different indicators and lung diseases, we successfully applied the naive Bayes model for a biomarker-based prediction of diagnosis and development into complex PF.ResultsMales predominantly marked their presence in all categories, save for complex PF where females took precedence. Biomarkers, specifically AGR, MLR, NLR, and PLR emerged as pivotal in discerning lung diseases. A machine-learning-driven predictive model underscored the efficacy of these markers in early detection and diagnosis, with NLR exhibiting unparalleled accuracy.ConclusionsOur study elucidates the gender disparities in lung diseases and illuminates the profound potential of serum biomarkers, including AGR, MLR, NLR, and PLR in early lung cancer detection. With NLR as a standout, therefore, this study advances the exploration of indicator changes and predictions in patients with pulmonary disease and fibrosis, thereby improving early diagnosis, treatment, survival rate, and patient prognosis.

Diagnostic Performance of CLEIA Versus FEIA for KL-6 Peripheral and Alveolar Concentrations in Fibrotic Interstitial Lung Diseases: A Multicentre Study.

Interstitial lung diseases (ILD) is a group of lung disorders characterized by interstitial lung thickening due to inflammatory and fibrotic processes. Krebs von den Lungen-6 (KL-6) is a molecule secreted by damaged type II alveolar pneumocytes in the alveolar space. The goal of the present study was to compare two detection methods of KL-6 in both bronchoalveolar lavage (BAL) and serum from ILD patients at the moment of diagnosis. Patients with suspicious of ILD and followed at two Italian referral centres for rare lung diseases were included in the study. BAL fluid and serum were collected and analysed by chemiluminescent enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) methods provided by Tosoh Biosciences. A total of 158 (mean age ± standard deviation, 61.5 ± 13.7, 65 females) patients were enrolled. A total of, 36 had diagnosis of idiopathic pulmonary fibrosis (IPF), 74 sarcoidosis, 15 connective tissue disease-ILD (CTD-ILD) and 33 other ILD. Diagnostic agreement between two methods was demonstrated for both BAL (r = 0.707, p < 0.0001) and serum (r = 0.816, p < 0.0001). BAL KL-6 values were lower than serum (p < 0.0001). IPF patients had higher serum KL-6 concentration than other ILDs (p = 0.0294), while BAL KL-6 values were lower in IPF than in non-IPF (p = 0.0023). This study explored KL-6 concentrations through the CLEIA method in serum and BAL of patients with various ILDs, showing significant differences of biomarkers concentrations between IPF and other non-IPF ILDs. Our findings are promising as they provided further knowledge concerning KL-6 expression across different ILDs and may suggest its utility in differential diagnosis.

Interstitial Lung Disease in Primary Sjögren's Syndrome: Risk factors for occurrence and radiographic progression.

The aim of this study is to investigate the characteristics of Primary Sjögren's syndrome (pSS)- interstitial lung disease (ILD) patients and compare them to those of pSS patients without ILD in the tertiary pSS-ILD cohort to evaluate potential risk factors for ILD occurrence and disease progression. Patients followed up who met the 2016 American College of Rheumatology-European League Against Rheumatism classification criteria for pSS were retrospectively analyzed. The patients were grouped as those with ILD and those without ILD according to medical records. High-resolution computed tomography (HRCT)/ thorax CT (TCT) results of all ILD patients were evaluated. Data on demographics, comorbidities, clinical characteristics and laboratory findings were collected. A total of 378 pSS patients, including 60 with ILD and 318 without ILD were detected to have at least one obtainable HRCT/TCT and were included in the study. In the cohort of pSS patients with at least one HRCT or TCT, the frequency of ILD was 15.8%. In the ILD group, the most common HRCT pattern was NSIP, and the most common findings were ground glass opacities, traction bronchiectasis, and honeycombing. Logistic regression analysis showed that male gender (OR:2.90), being diagnosed with pSS over the age of 50(OR:4,24), smoking history (OR:2.38), elevated LDH(OR:3.27), elevated ESR(OR:2.51) and lymphopenia (OR:5.12) were related with development of ILD while being diagnosed with ILD after the age of 60 (OR:8.5) was related with radiographic progression. The study results provided a large spectrum view for pSS-ILD and pointed out several risk factors for ILD occurrence and radiographic progression.

Implications of the 2022 lung function update and GLI global reference equations among patients with interstitial lung disease

BackgroundLung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and...

The management of Familial Pulmonary Fibrosis in different medical settings: Where does that leave us? An Italian nationwide survey.

Familial Pulmonary Fibrosis (FPF) is an emerging group of interstitial lung diseases (ILDs) caused by mutations mainly involving "telomere-related genes" and "surfactant-related genes". Although, in 2023, European Respiratory Society proposed a statement for FPFs management, these still remain a burden. Our work aimed to evaluate the management and impact of FPF in three Italian different medical settings: University Hospitals (UHs), non-University Hospitals (N-UHs) and outpatient clinics. This survey was created by ILDs Study Group Società Italiana di Pneumologia/ Italian Respiratory Society (SIP-IRS) and diffused via email to all SIP-IRS members. The descriptive statistical analysis was conducted through GraphPad Prism software (version 8.0). Results: Twenty participants replied to the survey, of which 65% (13/20) worked at UH while the remaining 25% (6/20) and 5% (1/20) worked at N-UH and outpatient clinics, respectively. Centers with, at least, 150 ILD patients visits/year followed a higher number of FPF patients, regardless of University affiliation (p=0.0046). Despite significant discrepancies in genetic testing and availability of counselling were registered, no statistically significant differences in patients' anamnesis assessment were observed between UHs and N-UHs (p=0.4192 and p=0.6525). However, there were relevant differences in the number of FPF patients undergoing genetic assessment in the Centers with Genetics Lab or Unit inside the Hospital (p=0.0253). There was no consensus regarding the impact of FPF diagnosis on lung transplantation and screening of asymptomatic relatives. Similarly, no differences were reported in antifibrotic prescriptions between UHs and N-UHs. Although the typical UIP pattern was the most common radiological pattern observed in FPF patients, there were no differences in the prevalence of histopathological patterns between UH and N-UH. Improving pulmonologists' knowledge of the approach, diagnosis and management of FPF is a global medical topic. Scientific societies can provide significant support in raising physicians' awareness of this issue.

Chemokine receptor CXCR4 based positron emission tomography imaging in systemic sclerosis-related interstitial lung disease.

To assess chemokine receptor CXCR4 expression in lung parenchyma and on peripheral immune cells in systemic sclerosis-related interstitial lung disease (SSc-ILD) patients. SSc-ILD patients underwent 68Ga- CPCR4 Trifluoroacetate positron emission tomography (PET) scan, SUVmean in different lung regions and architecturally abnormal areas, and receiver operating characteristic (ROC) curves were analyzed. CXCR4 expression on peripheral immune cells using flow cytometer was studied and correlated with the different lung regions. In addition, subset analysis of CXCR4 expression by clinical subset (early, progressive, stable), ILD pattern and anti-Scl-70 positivity were done. On PET, SSc-ILD patients showed higher median SUVmean uptake of CXCR4 in the whole lung (0.56; p< 0.0001), different lung regions and architecturally abnormal areas than controls. Highest area under curve (AUC) were observed in dorsobasal regions (AUC-0.91; p< 0.0001) and reticular with architecturally distorted areas (AUC-0.95; p< 0.0001). Progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; p< 0.0001) and stable (0.45; p< 0.0001) subsets, and AUC than early and stable subsets. Usual interstitial pneumonia pattern ILD showed higher CXCR4 uptake compared with non-specific interstitial pneumonia (p= 0.0032). Additionally, a trend for higher uptake was noted in anti-Scl70 positive patients as compared with anti-Scl70 negative ones. SSc-ILD patients had higher CD4+CXCR4+T cells (p= 0.0003), and CD8+CXCR4+T cells (p= 0.0013), and showed moderate to strong association on correlation with the lung parenchymal regions. In SSc-ILD, CXCR4 expression is upregulated in both lung parenchyma and peripheral T cells, significantly in progressive and UIP subsets. CXCR4 expression is a potential tool for activity assessment and prognostication.

Nintedanib in the treatment of interstitial lung disease in patients with systemic connective tissue diseases

Nintedanib in the treatment of interstitial lung disease in patients with systemic connective tissue diseases