Idiopathic Interstitial Lung Disease Research Articles

HRCT findings predict 1-year mortality in patients with acute exacerbation of idiopathic inflammatory myopathies-associated interstitial lung disease

BackgroundAcute exacerbation of idiopathic inflammatory myopathies-associated interstitial lung disease (AE-IIM-ILD) is a significant event associated with increased morbidity and mortality. However, few studies investigated the potential prognostic factors contributing to mortality in patients who experience AE-IIM-ILD. ObjectivesThe purpose of our study was to comprehensively investigate whether high-resolution computed tomography (HRCT) findings predict the 1-year mortality in patients who experience AE-IIM-ILD. MethodsA cohort of 69 patients with AE-IIM-ILD was retrospectively created. The cohort was 79.7% female, with a mean age of 50.7. Several HRCT features, including total interstitial lung disease extent (TIDE), distribution patterns, and radiologic ILD patterns, were assessed. A directed acyclic graph (DAG) was used to evaluate the statistical relationship between variables. The Cox regression method was performed to identify potential prognostic factors associated with mortality. ResultsThe HRCT findings significantly associated with AE-IIM-ILD mortality include TIDE (HR per 10%-increase, 1.64; 95%CI, 1.29–2.1, p < 0.001; model 1: C-index, 0.785), diffuse distribution pattern (HR, 3.75, 95%CI, 1.5-9.38, p = 0.005; model 2: C-index, 0.737), and radiologic diffuse alveolar damage (DAD) pattern (HR, 6.37, 95% CI, 0.81-50.21, p = 0.079; model 3: C-index, 0.735). TIDE greater than 58.33%, diffuse distribution pattern, and radiologic DAD pattern correlate with poor prognosis. The 90-day, 180-day, and 1-year survival rates of patients who experience AE-IIM-ILD were 75.3%, 66.3%, and 63.3%, respectively. ConclusionHRCT findings, including TIDE, distribution pattern, and radiological pattern, are predictive of 1-year mortality in patients who experience AE-IIM-ILD.

P149 Association between nailfold videocapillaroscopy findings and sKL-6 levels in patients with idiopathic inflammatory myopathies-related interstitial lung disease

Abstract Background/Aims Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired muscle diseases with distinct clinical, pathological and histological features. Interstitial lung disease (ILD) is a frequent pulmonary manifestation in IIM (IIM-ILD) and considerably influences morbidity and mortality. Krebs von den Lungen 6 (sKL-6) has been proposed as a potential biomarker reflecting the severity of ILD in connective tissue diseases. Raynaud’s phenomenon is very frequent and the presence of microvascular changes in IIM have been described however, the role of nailfold videocapillaroscopy (NVC) in diagnosis and prognosis in IIM is not clearly established. We aim to determine if there is any association between NVC findings, sKL-6 levels and pulmonary involvement in patients with inflammatory myopathies. Methods We performed a retrospective study of IIM patients followed in a reference center and compared them according to the presence of ILD. Epidemiological, clinical and immunological data, pulmonary function tests (forced vital capacity and diffusing capacity for carbon monoxide), sKL-6 levels and NVC finding were retrieved. Statistical analysis was performed by T-test and Fisher’s exact test to compare qualitative and/or quantitative variables and multiple logistic regression modelling to identify correlation between pulmonary function tests, NVC findings and sKL-6 levels. Results 95 patients were included, 47 patients (49%) with ILD. 34% were male with a median age at inclusion of 55.3±24 years. Avascular areas and capillary lossshowed a significant association with the presence of ILD (OR 2.43, 95% CI 1.3-5.7, p 0.004) and (OR 1.7, 95% CI 1.48-3.1, p 0.04). A negative correlation between capillary loss and enlarged capillaries was also found with FVC% (β=-0.46, p 0.001 and β=-0.57, p &amp;lt; 0.0001) and DLCO% (β=-0.32, p 0.04 and β=- 0.23, p 0.03), respectively. When we studied the correlation between sKL-6 levels, positive correlations with the presence of ILD (β = 0.77, p 0.0004), the presence of hemorrhages (β = 0.21, p 0.04) and avascular areas in NVC (β = 0.64, p 0.03) and negative correlations with FVC% (β=-0.47, p 0.001) and DLCO% (β=-0.59, p, 0.005) were found. Male sex, respiratory symptoms, %FVC and %DLCO, sKL-6 levels, anti-Jo1 positivity and the presence of avascular areas and enlarged capillaries in NVC were identified as IIM-ILD predictors (R2=0.974, p = 0.006). Conclusion Capillary loss and avascular areas showed a significant association with the presence of ILD, worse FVC and DLCO values and sKL-6 levels. We identified nine predictors for developing ILD in IIM. NVC assessment and sKL-6 levels can have a predictive role for studying pulmonary function and assessing the prognosis of IIM-ILD. Disclosure C. Sieiro Santos: None. J. Tandaipan: None. D. Castillo: None. L. Martínez Martínez: None. H. Codes: None. L. Sainz: None. B. Magallares: None. P. Moya: None. H. Corominas: None. E. Díez Álvarez: None. I. Castellvi: None.

Microbiome features in bronchoalveolar lavage fluid of patients with idiopathic inflammatory myopathy-related interstitial lung disease.

Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with “idiopathic” interstitial lung disease

BackgroundAutoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. Methods499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. Results2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. ConclusionSpecific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Myositis-associated interstitial lung disease

Introduction/ObjectiveTo review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. Materials and methodsThe relevant literature was reviewed. ResultsThe clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. ConclusionDespite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD.

Clinical Features and Outcomes of Patients with Idiopathic Inflammatory Myositis-Associated Interstitial Lung Disease in Rural Appalachia: A Cross-Sectional Study.

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders often complicated by interstitial lung disease (ILD). The clinical characteristics and outcomes of IIM-associated ILD have been reported variably, but the literature on rural populations is scarce. A retrospective cross-sectional study was conducted at a rural tertiary academic medical center. Twenty-nine patients met the final inclusion criteria. The primary outcome was to assess the disease state and immunological and radiographic features of IIM-associated ILD. Secondary outcomes included disease progression, ILD exacerbation, mortality rate, and factors associated with poor outcome. Dermatomyositis (n = 15, 51.72%) followed by polymyositis (n = 8, 27.58%) were predominant myopathies. The most common autoantibodies were anti-Jo1 antibodies (n = 11, 37.93%). Indeterminate usual interstitial pneumonitis (41.30%, n = 12) was the most common radiographic pattern followed by non-specific interstitial pneumonia (n = 5, 17.24%). ILD exacerbation (n = 14, 66.66%) and mortality rate (n = 6, 20.69%) were high. Albumin levels were significantly lower in patients who died. The clinical characteristics of patients with IIM-associated ILD in rural Appalachia exhibit notable distinctions, and outcomes are worse compared to other populations. Larger studies are needed to investigate other prognostics factors and longitudinal trends of clinical characteristics and outcomes of IIM-associated ILD in rural populations.

Surgical outcomes and perioperative risk factors of patients with interstitial lung disease after pulmonary resection

BackgroundPatients of interstitial lung disease (ILD) combined with pulmonary lesions are increasingly common in clinical practice. Patients with ILD are at significantly higher risk for complications after pulmonary resection (including lobectomy and sublobar resection), especially acute exacerbations of ILD (AE-ILD). The purpose of this study is to summarize the short-term and long-term outcomes after pulmonary resection in ILD patients and to analyze the clinical factors affecting surgical safety.MethodsFrom January 2004 to January 2022, a total of 78 patients who were diagnosed with ILD and underwent pulmonary resection at our center were enrolled in this study. Clinical data, pathological findings, surgical procedures, and intraoperative safety of these patients were collected retrospectively. Postoperative 90-day complications and mortality, long-term surgical outcomes from postoperative 90 days to 24 months, and changes in ILD condition were investigated. Logistic regression analysis was used to identify the risk factors associated with postoperative complications.ResultsThe median age of patients was 66.5 (range 33–86) years, 82.1% (64/78) of patients were male, and 78.2% (61/78) of patients had comorbidities. Idiopathic ILD and secondary ILD accounted for 86% and 14%, thoracotomy and video-assisted thoracoscopic surgery accounted for 12.8% and 87.2%, and lobectomy and sublobar resection accounted for 37.2% and 62.8%, respectively. Postoperative 90-day complications occurred in 25.6% (20/78) of patients, with pulmonary complications and AE-ILD occurring in 15.4% and 9.0% of patients, respectively. The postoperative 90-day mortality rate was 5.1% (4/78), and the cause of death was AE-ILD. Exacerbation of ILD or other complications occurred in 12.8% (10/78) of patients from postoperative 90 days to 24 months. Univariate logistic regression analysis showed that comorbidity, extent of resection, systemic lymph node dissection, operation time, intraoperative blood loss, and pathology of pulmonary lesion were associated with postoperative 90-day complications. In multivariate logistic regression analysis, age-adjusted Charlson Comorbidity Index and intraoperative blood loss were identified as independent risk factors of postoperative 90-day complications.ConclusionsPatients with ILD have a significantly higher risk of postoperative 90-day complications and mortality after pulmonary resection, especially pulmonary complications and AE-ILD. After postoperative 90 days, the risk of deterioration of pulmonary status remains high, including exacerbation of ILD and complications associated with long-term use of glucocorticoids and immunosuppressant. Age, comorbidity and intraoperative blood loss are high risk factors for postoperative 90-day complications.

Progression prediction in idiopathic inflammatory myopathy-associated interstitial lung disease: a combination of initial high attenuation areas and anti-melanoma differentiation-associated gene 5-positive.

To analyse quantitative lung densitometry and clinical baseline data of individuals with idiopathic inflammatory myopathy (IIM) and identify risk factors capable of predicting the progression of interstitial lung disease (ILD). We utilised quantitative lung densitometry and clinical baseline data as explanatory variables. Univariate and multivariate Cox regression analyses were employed to pinpoint effective risk factors for predicting ILD progression in IIM patients. The findings from the Cox univariate regression analysis indicate that elevated carcinoembryonic antigen levels (HR=1.036, 95% CI 1.004-1.069) are connected to an elevated risk of ILD progression in patients with IIM (P=0.027), while PO2 (HR=0.980, 95% CI 0.962-0.997) , forced vital capacity (HR=0.551, 95% CI 0.320-0.946) are protective factors for ILD progression in patients with IIM (p=0.025, p=0.031, respectively), anti-EJ positivity (HR=0.399, 95% CI 0.175-0.912) and anti-Ro52 positivity (HR=0.437, 95% CI 0.199-0.960) are risk factors for ILD progression in patients with IIM (p=0.029, p=0.039, respectively). Furthermore, the results of Cox multivariate regression analysis reveal that high attenuation areas (HAA) (>465.745 cm3) (HR=5.007, 95% CI 1.773-14.144) and anti-melanoma differentiation-associated gene 5 (Anti-MDA5) positivity (HR=0.127, 95% CI 0.041-0.396) are autonomous prognostic risk factors for ILD progression in individuals with IIM (p=0.002, p<0.001, respectively). Among IIM patients, those who are anti-MDA5-positive, and exhibit HAA (>465.745cm3) are more likely to experience ILD progression.

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

BackgroundDrug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need.MethodsBiomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls.ResultsSerum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients.ConclusionsThe serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

Identifying the link between serum VEGF and KL-6 concentrations: a correlation analysis for idiopathic pulmonary fibrosis interstitial lung disease progression.

Idiopathic pulmonary fibrosis interstitial lung disease (IPF-ILD) is a progressive lung disease characterized by excessive collagen deposition and fibrotic changes in the lungs. Identifying reliable serum markers that correlate with disease progression is crucial for diagnosis and prognosis. This study aimed to explore the association between serum markers KL-6 and VEGF and IPF-ILD. Specifically, it assessed their correlation with PaO2, a measure of pulmonary gas function, to provide diagnostic and prognostic indicators. Patients with IPF-ILD were included, and their serum levels of KL-6 and VEGF were measured. Correlations with fibrotic damage and PaO2 were analyzed using statistical methods. The analysis confirmed a positive correlation between the serum marker KL-6 and the degree of fibrotic damage in IPF-ILD. On the other hand, the serum marker VEGF was found to promote disease progression. In terms of correlation with PaO2, both KL-6 and VEGF demonstrated high sensitivity and specificity. Specifically, the correlation between KL-6 and PaO2 suggests that it can be used as a reliable indicator to assess the status of pulmonary oxygenation function in patients with ILD. The correlation between VEGF and PaO2 helps to understand its role in the progression of IPF-ILD and provides an important basis for predicting patient prognosis. This study confirmed the correlation between KL-6 and VEGF with IPF-ILD and their association with PaO2. KL-6 and VEGF demonstrated high specificity and sensitivity in diagnosing, monitoring, and predicting prognosis in IPF-ILD. These findings contribute to our understanding of the disease and have clinical implications for diagnosis and prognostication.

Myositis-associated interstitial lung disease

Introduction/ObjectiveTo review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. Materials and methodsThe relevant literature was reviewed. ResultsThe clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. ConclusionDespite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD.

Establishment and application of the BRP prognosis model for idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information.MethodsA multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the “BRP Prognosis Model”. The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed.ResultsNeutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2–3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration.ConclusionsIn this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.

U-net convolutional neural network applied to progressive fibrotic interstitial lung disease: Is progression at CT scan associated with a clinical outcome?

BackgroundComputational advances in artificial intelligence have led to the recent emergence of U-Net convolutional neural networks (CNNs) applied to medical imaging. Our objectives were to assess the progression of fibrotic interstitial lung disease (ILD) using routine CT scans processed by a U-Net CNN developed by our research team, and to identify a progression threshold indicative of poor prognosis. MethodsCT scans and clinical history of 32 patients with idiopathic fibrotic ILDs were retrospectively reviewed. Successive CT scans were processed by the U-Net CNN and ILD quantification was obtained. Correlation between ILD and FVC changes was assessed. ROC curve was used to define a threshold of ILD progression rate (PR) to predict poor prognostic (mortality or lung transplantation). The PR threshold was used to compare the cohort survival with Kaplan Mayer curves and log-rank test. ResultsThe follow-up was 3.8 ± 1.5 years encompassing 105 CT scans, with 3.3 ± 1.1 CT scans per patient. A significant correlation between ILD and FVC changes was obtained (p = 0.004, ρ = -0.30 [95% CI: -0.16 to -0.45]). Sixteen patients (50%) experienced unfavorable outcome including 13 deaths and 3 lung transplantations. ROC curve analysis showed an aera under curve of 0.83 (p < 0.001), with an optimal cut-off PR value of 4%/year. Patients exhibiting a PR ≥ 4%/year during the first two years had a poorer prognosis (p = 0.001). ConclusionsApplying a U-Net CNN to routine CT scan allowed identifying patients with a rapid progression and unfavorable outcome.

Association between the Lung Immune Prognostic Index and mortality in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

Objective: To explore the association between the Lung Immune Prognostic Index (LIPI) and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease (IIM-ILD). Methods: Patients who were diagnosed with IIM-ILD at West China Hospital, Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI. Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients' mortality. Results: A total of 1116 patients were screened, and 830 were included in this study. The multivariable Cox analysis showed that, compared with patients with poor LIPI, the hazard ratio (HR) for all-cause 1-year mortality was 0.22 (95% CI 0.05-0.93, P=0.04) for patients in the good LIPI group (LDH&lt;250 IU/L and dNLR&lt;3). After excluding patients lost to follow-up within one year, a similar result was found for LIPI (HR 0.20, 95% CI 0.05-0.86; P=0.03). Conclusions: Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD. This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.

Burden of Disease and Productivity Loss in the European Economic Area in Patients Affected by Fibrosing Interstitial Lung Disease.

Progression of fibrosis in interstitial lung diseases (ILD) has been associated with poor prognosis, lower quality of life for patients and caregivers, and higher healthcare costs. This study estimated the burden of disease and productivity loss of progressively fibrosing ILD, focusing on progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (non-IPF PPF) and systemic sclerosis-associated ILD (SSc-ILD) in the European Economic Area (EEA). An economic model was built to estimate the clinical burden of SSc-ILD and non-IPF PPF. The model was based on published data on disease prevalence and disease burden (in terms of comorbidities, exacerbations, and deaths) as well as on productivity loss (in terms of sick days, early retirement, permanent disability, and job loss). Aggregate income loss was obtained by multiplying productivity loss by the median daily income in each country/area of investigation. A sensitivity analysis was performed to test the impact of the variability of the model assumptions. In the whole EEA, a total of 86,794 and 13,221 individuals were estimated to be affected by non-IPF PPF and SSc-ILD, respectively. Estimated annual sick days associated with the diseases were 3,952,604 and 672,172, early retirements were 23,174 and 5341, permanently disabled patients were 41,748 and 4037, and job losses were 19,789 and 2617 for non-IPF PPF and SSc-ILD, respectively. Annual exacerbations were estimated to be 22,401-31,181 and 1259-1753, while deaths were 5791-6171 and 572-638 in non-IPF PPF and SSc-ILD, respectively. The estimated annual aggregate income loss in EEA, accounting for losses due to annual sick days, early retirements, and permanently disabled patients, was €1433 million and €220 million in non-IPF PPF and SSc-ILD, respectively. The productivity loss due to job losses was €194 million and €26 million in non-IPF PPF and SSc-ILD, respectively. The main driver of aggregate income loss variability was the prevalence. The impact of non-IPF PPF and SSc-ILD on society is definitely non-negligible. Actions to reduce the burden on our societies are highly needed.

Surgical Treatment of Secondary Pneumothorax-Complicated Interstitial Lung Disease.

To investigate the feasibility of early surgical treatment and perioperative steroid use in patients with interstitial lung disease (ILD) complicated by pneumothorax. We retrospectively examined data, including patient characteristics, laboratory findings, surgical treatment details, postoperative complications, and deaths, of nine patients with ILD complicated by secondary pneumothorax. The patients had been treated at our hospital during the past 10 years. All nine patients were male (median age, 69.0 years). A total of nine patients had a histopathologic diagnosis of ILD after surgery. Of these, five were clinically diagnosed with ILD before surgery. Collagen disease was diagnosed in one case, drug-induced in one case, and idiopathic ILD (IILD) in three cases. All nine patients were diagnosed with postoperative ILD, including one case of collagen disease, one case of drug-induced, three cases of idiopathic pulmonary fibrosis (IPF)/cryptogenic fibrosing alveolitis, one case of nonspecific interstitial pneumonia (NSIP), and three cases of cryptogenic organizing pneumonia (COP). Regarding preoperative clinical characteristics, the performance status (PS) was 0 or 1 in all patients. Overall, three patients received oxygen (0-3 L/min), whereas steroids were administered to five patients. The mean drainage period was 23.5 days, and this was consistent with the time taken from pneumothorax occurrence to surgery. Video-assisted thoracic surgery (VATS) and thoracoscopic-assisted surgery were performed in seven and two patients, respectively. No postoperative recurrence or surgery-related deaths occurred. Early surgery for secondary pneumothorax complicated by ILD may be a viable option for patients in good preoperative condition. For patients who are preoperatively treated with steroids, continued use of steroids should be carefully considered.

Desquamative interstitial pneumonia: If there is smoke there is fire

Desquamative interstitial pneumonia (DIP) is a rare type of idiopathic interstitial lung disease (ILD) predominantly seen in smokers. Connective tissue diseases (CTDs) are one of the important causes of ILD and may have lung involvement antedating their usual manifestations, making the diagnosis difficult. Interstitial pneumonia with autoimmune features (IPAFs) are ILDs having autoimmune features but not fulfilling the criteria for a definite CTD. A small minority of IPAF cases may progress to CTD–related ILD over a period. Usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia are common radiological and histopathological patterns associated with IPAF. DIP is a rare manifestation of IPAF. Patients with IPAF and a non-UIP pattern may benefit from immunomodulation. We present a rare case of DIP in a nonsmoker, who was initially labeled as idiopathic ILD but eventually evolved into IPAF and exhibited a good response to immunosuppressive treatment.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects

ObjectiveNintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects.MethodsPatients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them.ResultsTwenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months—p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months—p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN.ConclusionWe presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

The interplay of physical and cognitive function in rehabilitation of interstitial lung disease patients: a narrative review.

Interstitial lung disease (ILD) encompasses several diverse pulmonary pathologies that result in abnormal diffuse parenchymal changes. When prescribing rehabilitation, several additional factors need to be considered as a result of aging, polypharmacy, and comorbidities manifested in ILD patients. This review aims to discuss issues related to frailty, skeletal muscle and cognitive function that limit physical activities in ILD patients. It will also highlight exercise training and propose complementary strategies for pulmonary rehabilitation. A literature search was performed in MEDLINE, CINAHL (inception to October 19th, 2022) using search terms based on concepts of: idiopathic pulmonary fibrosis or interstitial lung disease; frailty; muscular atrophy; skeletal muscle dysfunction; cognitive dysfunction; sleep quality; sleep disorders; anxiety disorders; or depressive disorders. After eligible texts were screened, additional references were included from references cited in the screened articles. Frailty and skeletal muscle dysfunction are common in ILD. Weight loss, exhaustion, and anti-fibrotic medications can impact frailty, whereas physical inactivity, aging, corticosteroids and hypoxemia can contribute to sarcopenia (loss of muscle mass and function). Frailty is associated with worse clinical status, exercise intolerance, skeletal muscle dysfunction, and decreased quality of life in ILD. Sarcopenia appears to influence wellbeing and can potentially affect overall physical conditioning, cognitive function and the progression of ILD. Optimal assessment tools and effective strategies to prevent and counter frailty and sarcopenia need to be determined in ILD patients. Even though cognitive impairment is evident in ILD, its prevalence and underlying neurobiological model of contributing factors (i.e., inflammation, disease severity, cardiopulmonary status) requires further investigation. How ILD affects cognitive interference, motor control and consequently physical daily activities is not well defined. Strategies such as pulmonary rehabilitation, which primarily focuses on strength and aerobic conditioning have demonstrated improvements in ILD patient outcomes. Future incorporation of interval training and the integration of motor learning could improve transfer of rehabilitation strategies to daily activities. Numerous underlying etiologies of ILD contribute to frailty, skeletal muscle and cognitive function, but their respective neurobiologic mechanisms require further investigation. Exercise training increases physical measures, but complementary approaches may improve their applicability to improve daily activities.

Mesenchymal Stem Cells Inhibit Epithelial-to-Mesenchymal Transition by Modulating the IRE1α Branch of the Endoplasmic Reticulum Stress Response.

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease, and it carries a poor prognosis due to a lack of efficient diagnosis methods and treatments. Epithelial-mesenchymal transition (EMT) plays a key role in IPF pathogenesis. Endoplasmic reticulum (ER) stress contributes to fibrosis via EMT-mediated pathways. Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for pulmonary fibrosis and ameliorates lung fibrosis in animal models via paracrine effects. However, the specific mechanisms underlying the effect of transplanted MSCs are not known. We previously reported that MSCs attenuate endothelial injury by modulating ER stress and endothelial-to-mesenchymal transition. The present study investigated whether modulation of ER stress- and EMT-related pathways plays essential roles in MSC-mediated alleviation of IPF. We constructed a A549 cell model of transforming growth factor-β1 (TGF-β1)-induced fibrosis. TGF-β1 was used to induce EMT in A549 cells, and MSC coculture decreased EMT, as indicated by increased E-cadherin levels and decreased vimentin levels. ER stress participated in TGF-β1-induced EMT in A549 cells, and MSCs inhibited the expression of XBP-1s, XBP-1u, and BiP, which was upregulated by TGF-β1. Inhibition of ER stress contributed to MSC-mediated amelioration of EMT in A549 cells, and modulation of the IRE1α-XBP1 branch of the ER stress pathway may have played an important role in this effect. MSC transplantation alleviated bleomycin (BLM)-induced pulmonary fibrosis in mice. MSC treatment decreased the expression of ER stress- and EMT-related genes and proteins, and the most obvious effect of MSC treatment was inhibition of the IRE1α/XBP1 pathway. The present study demonstrated that MSCs decrease EMT by modulating ER stress and that blockade of the IRE1α-XBP1 pathway may play a critical role in this effect. The current study provides novel insight for the application of MSCs for IPF treatment and elucidates the mechanism underlying the preventive effects of MSCs against pulmonary fibrosis.