Usual Interstitial Pneumonia Pattern Research Articles

Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study.

A usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors. We used two-sample bidirectional Mendelian randomisation (MR) to test the hypothesis of a causal effect of RA on UIP and of UIP on RA, using variants from genome-wide association studies (GWAS) of RA (separately for seropositive (18 019 cases and 991 604 controls) and seronegative (8515 cases and 1 015 471 controls) RA) and of IPF (4125 cases and 20 464 controls) as genetic instruments. Sensitivity analyses were conducted to assess the robustness of the results to violations of the MR assumptions. IPF showed a significant causal effect on seropositive RA, with developing IPF increasing the risk of seropositive RA (OR=1.06, 95% CI: 1.04 to 1.08, p<0.001) which was robust under all models. For the MR in the other direction, seropositive RA showed a significant protective effect on IPF (OR=0.93; 95% CI: 0.87 to 0.99; p=0.032), but the effect was not significant when sensitivity analyses were applied. This was likely because of bias due to exclusion of patients with RA from among the cases in the IPF GWAS, or possibly because our genetic instruments did not fully capture the effect of the complex human leucocyte antigen region, the strongest RA genetic risk factor. Our findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between UIP and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The significant causal effect of IPF on seropositive RA suggests that pathomechanisms involved in the development of UIP may promote RA, and this may help inform future guidelines on screening for ILD in patients with RA.

A Machine Learning System to Indicate Diagnosis of Idiopathic Pulmonary Fibrosis Non-Invasively in Challenging Cases.

Radiologic usual interstitial pneumonia (UIP) patterns and concordant clinical characteristics define a diagnosis of idiopathic pulmonary fibrosis (IPF). However, limited expert access and high inter-clinician variability challenge early and pre-invasive diagnostic sensitivity and differentiation of IPF from other interstitial lung diseases (ILDs). We investigated a machine learning-driven software system, Fibresolve, to indicate IPF diagnosis in a heterogeneous group of 300 patients with interstitial lung disease work-up in a retrospective analysis of previously and prospectively collected registry data from two US clinical sites. Fibresolve analyzed cases at the initial pre-invasive assessment. An Expert Clinical Panel (ECP) and three panels of clinicians with varying experience analyzed the cases for comparison. Ground Truth was defined by separate multi-disciplinary discussion (MDD) with the benefit of surgical pathology results and follow-up. Fibresolve met both pre-specified co-primary endpoints of sensitivity superior to ECP and significantly greater specificity (p = 0.0007) than the non-inferior boundary of 80.0%. In the key subgroup of cases with thin-slice CT and atypical UIP patterns (n = 124), Fibresolve's diagnostic yield was 53.1% [CI: 41.3-64.9] (versus 0% pre-invasive clinician diagnostic yield in this group), and its specificity was 85.9% [CI: 76.7-92.6%]. Overall, Fibresolve was found to increase the sensitivity and diagnostic yield for IPF among cases of patients undergoing ILD work-up. These results demonstrate that in combination with standard clinical assessment, Fibresolve may serve as an adjunct in the diagnosis of IPF in a pre-invasive setting.

Characteristics of chest high-resolution computed tomography in patients with anti-aminoacyl-tRNA synthetase antibody-positive interstitial lung disease.

Anti-aminoacyl-tRNA synthetase (ARS) antibodies form a condition called Antisynthetase syndrome (ASSD). While interstitial lung disease (ILD) is a particularly frequent manifestation of ASSD and is closely associated with morbidity and mortality, few studies have been conducted on its characteristics on high-resolution computed tomography (HRCT). In this study, we clarified the HRCT findings in patients with anti-ARS antibody-positive ILD (ARS-ILD). Methods: The HRCT findings at the time of the ILD diagnosis in 24 ARS-ILD patients were retrospectively evaluated by 2 pulmonologists and one radiologist. We also assessed the clinical symptoms, physical examination findings, and laboratory data including the type of anti-ARS antibodies. For a further analysis, the data of patients were divided into two groups: the polymyositis (PM)/dermatomyositis (DM) group and the non-PM/DM group. The ratio of men to women was almost 1:1. The median age at the time of the diagnosis was 53 years old. Anti-glycyl (anti-EJ) and anti-histidyl (anti-Jo-1) antibodies were more common than others. An analysis of the HRCT patterns of 23 ARS-ILD patients showed that the most common pattern was the nonspecific interstitial pneumonia (NSIP) pattern. The second most common pattern was the usual interstitial pneumonia (UIP) pattern. Between the PM/DM and non-PM/DM groups, no clear trends were noted in the age, sex ratio, proportion of HRCT patterns, or type of anti-ARS antibodies. This retrospective study demonstrated that ARS-ILD patients, regardless of myositis symptoms, most often showed the NSIP pattern on HRCT, as previously reported. However, unlike previous reports, the UIP pattern on HRCT was not rare.

Overview of Rheumatoid Arthritis-Associated Interstitial Lung Disease and Its Treatment.

Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indicators are largely byproducts of prior ILD progression, including low or decreasing forced vital capacity and extensive or worsening fibrosis on imaging. In the absence of validated tools to predict treatment response, decisions about whether to initiate or augment treatment are instead based on clinical judgment. In general, treatment should be initiated in patients who are symptomatic, progressing, or at high risk of poor outcomes. Retrospective data suggest that mycophenolate mofetil, azathioprine, and rituximab are likely effective therapies for RA-ILD. Abatacept is also emerging as a potential first-line treatment option for patients with RA-ILD. Further, recent data demonstrate that immunosuppression may be beneficial even in patients with a usual interstitial pneumonia (UIP) pattern on imaging, suggesting that immunosuppression should be considered irrespective of imaging pattern. Recent randomized controlled trials have shown that antifibrotic medications, such as nintedanib and likely pirfenidone, slow forced vital capacity decline in RA-ILD. Consideration can be given to antifibrotic initiation in patients progressing despite immunosuppression, particularly in patients with a UIP pattern. Future research directions include developing tools to predict which patients will remain stable from patients who will progress, discriminating patients who will respond to treatment from nonresponders, and developing algorithms for starting immunosuppression, antifibrotics, or both as first-line therapies.

The diagnosis and treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease (ILD) of unknown cause. The prognosis of IPF is poor, respiratory failure is the most common cause of mortality. Velcro rales are typical on respiratory system examination. Clubbing is seen in 30-60% of IPF cases. There is no laboratory test specific to IPF. Usual interstitial pneumonia (UIP) pattern is seen in IPF. UIP features in high-resolution computed tomography (HRCT); peripheral subpleural bibasilar reticular opacities, honeycombing, traction bronchiectasis and interseptal thickening. It shows craniocaudal localization. Diagnosis of IPF; It is diagnosed by the combination of HRCT findings and clinical findings. Antifibrotic drugs (Pirfenidone and Nintedanib) slow down the progression of IPF and reduce the number of annual attacks and reduce the frequency of hospitalization.

Radiological usual interstitial pneumonia pattern is associated with two-year mortality in patients with idiopathic pulmonary fibrosis

IntroductionThe new diagnostic guidelines for idiopathic pulmonary fibrosis (IPF) did not rule out the possibility of combining the radiological patterns of usual interstitial pneumonia (UIP) and probable UIP, given the similar management and diagnostic capacity. However, the prognostic implications of these patterns have not been fully elucidated, with different studies showing heterogeneous results. We applied the new criteria to a retrospective series of patients with IPF, assessing survival based on radiological patterns, findings, and their extension. MethodsTwo thoracic radiologists reviewed high-resolution computed tomography images taken at diagnosis in 146 patients with IPF, describing the radiological findings and patterns. The association of each radiological finding and radiological patterns with two-year mortality was analysed. ResultsThe two-year mortality rate was 40.2% in IPF patients with an UIP radiological pattern versus 7.1% in those with probable UIP. Compared to the UIP pattern, probable UIP was protective against mortality, even after adjusting for age, sex, pulmonary function, and extent of fibrosis (hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.06–0.99). Receiving antifibrotic treatment was also a protective factor (HR 0.51, 95%CI 0.27–0.98). Honeycombing (HR 3.62, 95%CI 1.27–10.32), an acute exacerbation pattern (HR 4.07, 95%CI 1.84–8.96), and the overall extent of fibrosis (HR 1.04, 95%CI 1.02–1.06) were predictors of mortality. ConclusionsIn our series, two-year mortality was higher in patients with IPF who presented a radiological pattern of UIP versus probable UIP on the initial scan. Honeycombing, an acute exacerbation pattern, and a greater overall extent of fibrosis were also predictors of increased mortality. The prognostic differences between the radiological pattern of UIP and probable UIP in our series would support maintaining them as two differentiated patterns.

RADIOLOGICAL EVALUATION OF INTERSTITIAL LUNG DISEASES ON HIGH-RESOLUTION COMPUTED TOMOGRAPHY IN TERTIARY CARE CENTER OF NORTH INDIA

Objective: This study assessed the various high-resolution computed tomography (HRCT) patterns of interstitial lung diseases (ILDs) and to differentially diagnose ILD based on their clinical findings and distribution patterns. Methods: The study was conducted in the Department of Radiodiagnosis, Government Medical College and Rajindra Hospital, Patiala, Punjab, India. Forty-three patients with clinical suspicion of ILD were enrolled in the study. HRCT scans of the chest were done in all the cases taken in the study. Results: The mean age (±he age group of 51–60 years. We found slight female preponderance with females accounting for 53.5% and males accounting for 46.5% of the caseload. The most common presenting complaint was dyspnea on exertion (83.7%) followed by cough in 69.8%. The most frequent HRCT finding was septal thickening (90.7%), followed by tractional bronchiectasis (83.7%), fibrotic changes (72.1%), ground-glass opacities (65.1%), and honeycombing (58.1%). Based on HRCT findings, the most common HRCT pattern was the typical usual interstitial pneumonia pattern (58.1%), followed by the non-specific interstitial pneumonia pattern. The final diagnoses were made based on clinic-radiological findings and by the exclusion of other possibilities. The most common ILD reported was idiopathic pulmonary fibrosis (39.5%), followed by connective tissue disorder-ILD (20.9%), and SR-ILD (13.9%). This is followed by idiopathic non-specific interstitial pneumonia (11.6%), hypersensitivity pneumonitis (6.9%), and cryptogenic organizing pneumonia (2.3%). Conclusion: HRCT is a valuable technique for evaluating various ILDs even when chest X-rays are normal. It can differentially diagnose ILDs based on their clinical findings and distribution patterns.

Thin-Section CT in the Categorization and Management of Pulmonary Fibrosis including Recently Defined Progressive Pulmonary Fibrosis.

While idiopathic pulmonary fibrosis (IPF) is the most common type of fibrotic lung disease, there are numerous other causes of pulmonary fibrosis that are often characterized by lung injury and inflammation. Although often gradually progressive and responsive to immune modulation, some cases may progress rapidly with reduced survival rates (similar to IPF) and with imaging features that overlap with IPF, including usual interstitial pneumonia (UIP)-pattern disease characterized by peripheral and basilar predominant reticulation, honeycombing, and traction bronchiectasis or bronchiolectasis. Recently, the term progressive pulmonary fibrosis has been used to describe non-IPF lung disease that over the course of a year demonstrates clinical, physiologic, and/or radiologic progression and may be treated with antifibrotic therapy. As such, appropriate categorization of the patient with fibrosis has implications for therapy and prognosis and may be facilitated by considering the following categories: (a) radiologic UIP pattern and IPF diagnosis, (b) radiologic UIP pattern and non-IPF diagnosis, and (c) radiologic non-UIP pattern and non-IPF diagnosis. By noting increasing fibrosis, the radiologist contributes to the selection of patients in which therapy with antifibrotics can improve survival. As the radiologist may be first to identify developing fibrosis and overall progression, this article reviews imaging features of pulmonary fibrosis and their significance in non-IPF-pattern fibrosis, progressive pulmonary fibrosis, and implications for therapy. Keywords: Idiopathic Pulmonary Fibrosis, Progressive Pulmonary Fibrosis, Thin-Section CT, Usual Interstitial Pneumonia © RSNA, 2024.

Factors influencing long-term outcomes in fibrotic interstitial lung disease (F-ILD) diagnosed through multidisciplinary discussion (MDD): a prospective cohort study

BackgroundThe diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD).MethodsWe included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender–age–physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model.ResultsWe enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0–2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28–85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07–15.5; p = 0.039) were significantly associated with overall mortality.ConclusionThe long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients.

Imaging of pulmonary fibrosis in children: A review, with proposed diagnostic criteria.

Computed tomography (CT) imaging findings of pulmonary fibrosis are well established for adults and have been shown to correlate with prognosis and outcome. Recognition of fibrotic CT findings in children is more limited. With approved treatments for adult pulmonary fibrosis, it has become critical to define CT criteria for fibrosis in children, to identify patients in need of treatment and those eligible for clinical trials. Understanding how pediatric fibrosis compares with idiopathic pulmonary fibrosis and other causes of fibrosis in adults is increasingly important as these patients transition to adult care teams. Here, we review what is known regarding the features of pulmonary fibrosis in children compared with adults. Pulmonary fibrosis in children may be associated with genetic surfactant dysfunction disorders, autoimmune systemic disorders, and complications after radiation, chemotherapy, transplantation, and other exposures. Rather than a basal-predominant usual interstitial pneumonia pattern with honeycombing, pediatric fibrosis is primarily characterized by reticulation, traction bronchiectasis, architectural distortion, or cystic lucencies/abnormalities. Ground-glass opacities are more frequent in children with fibrotic interstitial lung disease than adults, and disease distribution appears more diffuse, without clearly defined axial or craniocaudal predominance. Following discussion and consensus amongst a panel of expert radiologists, pathologists and physicians, distinctive disease features were integrated to develop criteria for the first global Phase III trial in children with pulmonary fibrosis.

The Impact of Occupational Exposures on the Risk of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic pulmonary disorder of unknown etiology that is characterized by a usual interstitial pneumonia pattern. Previous meta-analyses have reported associations between occupational exposures and IPF, but higher-quality studies have been published in recent years, doubling the number of studied patients. Objectives: To provide a contemporary and comprehensive assessment of the relationship between occupational exposures and IPF. Methods: We searched PubMed, Embase, and Web of Science through July 2023 to identify all publications on occupational exposure and IPF. We conducted a meta-analysis of the occupational burden, odds ratio (OR), and population attributable fraction (PAF) of exposures. Five exposure categories were analyzed: vapors, gas, dust, and fumes (VGDF); metal dust; wood dust; silica dust; and agricultural dust. A comprehensive bias assessment was performed. The study protocol was registered in the International Prospective Register of Systematic Reviews (identifier CRD42021267808). Results: Our search identified 23,942 publications. Sixteen publications contained relative risks needed to calculate pooled ORs and PAFs, and 12 additional publications reported an occupational burden within a case series. The proportion of cases with occupational exposures to VGDF was 44% (95% confidence interval [CI], 36-53%), with a range of 8-17% within more specific exposure categories. The pooled OR was increased for VGDF at 1.8 (95% CI, 1.3-2.4), with a pooled PAF of 21% (95% CI, 15-28%). ORs and PAFs, respectively, were found to be 1.6 and 7% for metal dust, 1.6 and 3% for wood dust, 1.8 and 14% for agricultural dust, and 1.8 and 4% for silica dust. The pooled ORs and PAFs within specific exposure categories ranged from 1.6 to 1.8 and from 4% to 14%, respectively. We identified some publication bias, but it was not sufficient to diminish the association between occupational exposures and IPF based on sensitivity analysis and bias assessment. Conclusions: Our findings indicate that 21% of IPF cases (or approximately one in five) could be prevented by removal of occupational exposure (alongside a pooled OR of 1.8). Additionally, 44% of patients with IPF report occupational exposure to VGDF. This meta-analysis suggests that a considerable number of cases of IPF are attributable to inhaled occupational exposures and warrant increased consideration in the clinical care of patients and future prevention efforts.

Interstitial Lung Disease Is Associated with Sleep Disorders in Rheumatoid Arthritis Patients.

To evaluate sleep disorders and associated factors in patients with rheumatoid-arthritis-associated interstitial lung disease (RA-ILD). We performed an observational study of 35 patients with RA-ILD (cases) and 35 age- and sex-matched RA patients without ILD (controls). We evaluated sleep disorders (Oviedo Sleep Questionnaire), positive psychological factors (resilience using the Wagnild and Young Resilience Scale, emotional intelligence using the 24-item Trait Meta-Mood Scale), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (36-item short-form survey), and fatigue (Functional Assessment of Chronic Illness Therapy Questionnaire). Other variables studied included the Charlson Comorbidity Index (CCI) and RA activity according to the DAS28-ESR. Compared to the controls, the cases were characterized by poorer sleep quality with a higher prevalence of insomnia (42% vs. 20%; p = 0.039), greater severity of insomnia (p = 0.001), and lower sleep satisfaction (p = 0.033). They also had poorer resilience and emotional recovery and more severe anxiety and depression. A diagnosis of ILD was the only factor independently associated with the three dimensions of sleep quality. The predictors of poorer sleep satisfaction in patients with RA-ILD were age (β = -0.379), DAS28-ESR (β = -0.331), and usual interstitial pneumonia pattern (β = -0.438). The predictors of insomnia were DAS28-ESR (β = 0.294), resilience (β = -0.352), and CCI (β = 0.377). RA-ILD is associated with significant sleep disorders. RA-ILD seems to be an independent risk factor for sleep alterations, with a greater impact on insomnia. Age, disease activity, and comorbidity also play a role in sleep disorders in patients with RA-ILD.

Up-regulation by overexpression of c-MET in fibroblastic foci of usual interstitial pneumonia.

Usual interstitial pneumonia (UIP) is the radiologic and histologic hallmark of idiopathic pulmonary fibrosis (IPF) and the commonest histologic pattern of other progressive fibrosing interstitial lung diseases (e.g., fibrotic hypersensitivity pneumonia). Analogous to lung cancer, activation of epithelial-to-mesenchymal transition (EMT) is one of the main molecular pathways recently identified by transcriptomic studies in IPF. Fibroblastic foci (FF) are considered the active/trigger component of UIP pattern. The proto-oncogene C-MET is a key gene among molecules promoting EMT against which several inhibitors are currently available or promising in ongoing studies on lung cancer. Twenty surgical cases of diffuse fibrosing interstitial lung diseases (fILD) with UIP pattern and FF-rich (17 IPF and 3 patients with fibrotic hypersensitivity pneumonia, fHP) were retrospectively selected. FF were manually microdissected and analysed for c-MET gene alterations (FISH amplification and gene hot-spot mutations Sanger sequencing) and tested with a c-MET companion diagnostic antibody (clone SP44 metmab) by immunohistochemistry. FF are characterized by upregulation of c-MET as shown by overexpression of the protein in 80% of cases, while no gene amplification by FISH or mutations were detected. C-MET upregulation of FF was observed either in IPF and fHP, with a tropism for the epithelial cell component only. Upregulation of c-MET in FF of ILD with UIP pattern further confirms the key role of the proto-oncogene c-MET in its pathogenesis, possibly representing an interesting and easily-detectable molecular target for selective therapy using specific inhibitors in future clinical trials, similar to lung cancer. It is reasonable to speculate that molecular alterations in FF can also be detected in FF by transbronchial cryobiopsy.

Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Periostin was investigated as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This prospective study measured serum monomeric and total periostin, Klebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) in 19 patients with RA-ILD, 20 RA without ILD, and 137 healthy controls (HC). All biomarkers were higher in RA-ILD than HC or RA without ILD. KL-6 accurately detected ILD in RA patients (area under curve [AUC] = 0.939) and moderately detected SP-D and monomeric and total periostin (AUC = 0.803, =0.767, =0.767, respectively). Monomeric and total periostin were negatively correlated with normal lung area and positively correlated with honeycombing, reticulation, fibrosis score, and the traction bronchiectasis grade but not inflammatory areas. Serum levels of SP-D, KL-6, and LDH did not correlate with the extent of those fibrotic areas on high-resolution CT. Serum monomeric and total periostin were higher in patients with RA-ILD with definite usual interstitial pneumonia pattern compared with other ILD patterns. Immunohistochemical analyses of biopsy or autopsy lung tissues from RA-ILD during the chronic phase and acute exacerbation showed that periostin was expressed in fibroblastic foci but not inflammatory or dense fibrosis lesions. Periostin is a potential biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for patients with RA-ILD.

Differential Diagnosis of Fibrotic Hypersensitivity Pneumonitis with Its Non-Fibrotic Phenotype and Usual Interstitial Pneumonia During High-Resolution Computed Tomography

Background. Diagnosis of hypersensitivity pneumonitis (HP) using high-resolution computed tomography (HRCT) is not an easy task. The most difficult aspects of the disease include differential diagnosis of its fibrotic (fHP) and non-fibrotic (nfHP) phenotypes, as well as their differentiation from usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis. The determination of fibrous changes at an early stage of development can significantly accelerate the beginning of antifibrotic therapy and improve the prognosis.Objective: to identify key HRCT signs for reliable differentiation of fHP and nfHP, to carry out differential diagnostics between fHP and UIP.Material and methods. The data of 73 patients with morphologically verified HP, in whom HRCT had been performed, were retrospectively analysed. In 21 patients, nfHP was determined, and in 52 patients fHP was identified. The comparison group consisted of 24 patients with a typical radiological UIP pattern. The analysis of the changes detected during HRCT was carried out by qualitative and semi-quantitative methods. The significance of qualitative differences in a sign manifestation was assessed by Fisher’s exact test, semi-quantitative differences were evaluated using Mann–Whitney test.Results. The results of the study allow to assume, that the presence and degree of manifestation of certain HRCT signs significantly differ between the selected groups of patients in qualitative and/or semi-quantitative terms. In cases of НP, the distribution of changes was mostly uniform and diffuse, with no clear predominance in certain lobes. In UIP, diffuse craniocaudal distribution took place, and in the axial plane, the changes were mainly subpleural in nature.Conclusion. Based on the results of the study, it can be assumed that fHP significantly differs from nfHP in such features as the presence and degree of manifestation of ground glass and honeycombing symptoms, reticular changes and traction bronchiectases. When comparing the fHP and UIP groups, the distinctive signs of fHP were centrilobular nodules, mosaic pattern, as well as diffuse axial sign distribution.

Fibrosing Progressive Interstitial Lung Disease in Rheumatoid Arthritis: A Multicentre Italian Study.

The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients. One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern. We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms' evaluation might underestimate the prevalence of progressive lung disease but increases the value of results.

Plasma LTBP2 as a potential biomarker in differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis: a pilot study.

Few biomarkers distinguish connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF). Latent transforming growth factor-β binding protein-2 (LTBP2), a secreted extracellular matrix protein, is involved in pulmonary fibrosis. However, the role of LTBP2 in differentially diagnosing CTD-ILD and IPF is unclear. In this study, enzyme-linked immunosorbent assays quantified plasma LTBP2 concentrations in 200 individuals (35 healthy controls, 42 CTD patients without ILD, 89 CTD-ILD patients, and 34 IPF patients). CTD-ILD and IPF were further classified based on chest imaging pattern and pulmonary function test results. Plasma LTBP2 levels were significantly elevated in the IPF group compared with the CTD-ILD group. ROC analysis further suggested the possible value of LTBP2 in differentially diagnosing CTD-ILD and IPF. Additionally, CTD-ILD patients with progressive lung fibrosis had higher plasma LTBP2 concentrations than those who did not. Similarly, patients with IPF developing acute exacerbation showed higher plasma LTBP2 levels than those with stable IPF. This is the first study showing that LTBP2 was closely associated with the usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated ILD (RA-ILD). Moreover, the optimal cutoff values of LTBP2 for distinguishing IPF from CTD-UIP/RA-UIP were 33.75 and 38.33ng/mL with an AUC of 0.682 and 0.681, respectively. Our findings suggest that plasma LTBP2 levels may differentially diagnose CTD-ILD and IPF, and assess their fibrotic activity. Additionally, clinical LTBP2 evaluation may be a great aid to identifying the presence of the UIP pattern in RA-ILD and to discriminating IPF from CTD-UIP, particularly RA-UIP.

Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study

BackgroundAlthough patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS.MethodsPartitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4–8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements.ResultsTen AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was − 4.3 [− 7.6– − 2.3] cmH2O and lung elastance (EL) 44 [40–51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3–1.5] cmH2O and EL to 49 [43–59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL.ConclusionsIn mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Development and validation of a CT-based deep learning algorithm to augment non-invasive diagnosis of idiopathic pulmonary fibrosis

RationaleNon-invasive diagnosis of idiopathic pulmonary fibrosis (IPF) involves identification of usual interstitial pneumonia (UIP) pattern by computed tomography (CT) and exclusion of other known etiologies of interstitial lung disease (ILD). However, uncertainty in identification of radiologic UIP pattern leads to the continued need for invasive surgical biopsy. We thus developed and validated a machine learning algorithm using CT scans alone to augment non-invasive diagnosis of IPF. MethodsThe primary algorithm was a deep learning convolutional neural network (CNN) with model inputs of CT images only. The algorithm was trained to predict IPF among cases of ILD, with reference standard of multidisciplinary discussion (MDD) consensus diagnosis. The algorithm was trained using a multi-center dataset of more than 2000 cases of ILD. A US-based multi-site cohort (n = 295) was used for algorithm tuning, and external validation was performed with a separate dataset (n = 295) from European and South American sources. ResultsIn the tuning set, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.87 (CI: 0.83–0.92) in differentiating IPF from other ILDs. Sensitivity and specificity were 0.67 (0.57–0.76) and 0.90 (0.83–0.95), respectively. By contrast, pre-recorded assessment prior to MDD diagnosis had sensitivity of 0.31 (0.23–0.42) and specificity of 0.92 (0.87–0.95). In the external test set, c-statistic was also 0.87 (0.83–0.91). Model performance was consistent across a variety of CT scanner manufacturers and slice thickness. ConclusionThe presented deep learning algorithm demonstrated consistent performance in identifying IPF among cases of ILD using CT images alone and suggests generalization across CT manufacturers.

Disease progression in patients with usual interstitial pneumonia and probable UIP patterns on computed tomography with various underlying etiologies: a retrospective cohort study.

Usual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia that is caused by different etiologies. This study aimed to investigate the transplant-free survival (TFS) and the decline in forced vital capacity (FVC) of the patients with UIP and probable UIP patterns on CT caused by various underlying conditions. A retrospective cohort study was conducted, enrolling patients with interstitial lung disease exhibiting a CT pattern consistent with UIP or probable UIP. Clinical and prognostic data of patients categorized by the etiology were compared. A total of 591 patients were included and classified into the following groups: idiopathic pulmonary fibrosis (IPF) (n = 320), connective tissue disease (CTD)-UIP (n = 229), asbestosis-UIP (n = 28), and hypersensitivity pneumonitis (HP)-UIP (n = 14). Advanced age, elevated levels of serum cytokeratin fraction 21-1 and percentage of neutrophils in bronchoalveolar lavage were observed in all groups. IPF patients showed a more rapid decline in FVC (133.9 mL/year) compared to CTD-UIP (24.5 mL/year, p = 0.001) and asbestosis-UIP (61.0 mL/year, p = 0.008) respectively. Sub-analysis of CTD-UIP revealed that patients with rheumatoid arthritis (RA)-UIP (88.1 mL/year) or antineutrophil cytoplasmic antibody-associated vasculitis (AAV)-UIP (72.9 mL/year) experienced a faster deterioration in FVC compared to those with primary Sjögren's syndrome (pSS)-UIP (25.9 mL/year, p < 0.05). Kaplan-Meier curves showed that IPF had the poorest TFS (median 55.9 months), followed by HP-UIP (57.5 months), CTD-UIP (66.7 months), and asbestosis-UIP (TFS not reached). RA-UIP or AAV-UIP did not exhibit any prognostic advantages compared to IPF, while asbestosis-UIP and pSS-UIP showed better survival rates. Patients with UIP caused by different underlying conditions share certain common features, but the trajectories of disease progression and survival outcomes differ.