Search Results (89)

Background and Objectives: Fibrosing interstitial lung diseases (ILDs) may predispose to neurocognitive impairment through chronic hypoxemia and systemic inflammation, yet data integrating pulmonary physiology, disease severity, and cognition are limited. We aimed to compare global cognitive performance between adults with fibrosing ILD and contemporaneous non-ILD clinic comparators, explore differences across ILD subtypes, and identify physiologic and clinical predictors of low MMSE scores. Materials and Methods: In this single-center cross-sectional study, 45 adults with fibrosing ILD and 32 non-ILD participants from university-affiliated pulmonology clinics completed the Mini-Mental State Examination (MMSE) and standardized lung function testing (including diffusing capacity, DLCO%). Comorbidity (Charlson index), inflammatory markers (C-reactive protein), and GAP (Gender–Age–Physiology) severity were recorded. Associations with MMSE and MMSE < 24 were examined using correlations and multivariable logistic regression. Results: Mean MMSE was lower in ILD than in non-ILD participants (23.9 ± 3.6 vs. 26.8 ± 2.8; p < 0.001), and MMSE < 24 occurred in 33.3% versus 12.5%, respectively. Within ILD, the usual interstitial pneumonia (UIP) pattern showed the lowest MMSE scores. DLCO% and total lung capacity correlated positively with MMSE (r = 0.44 and r = 0.34, respectively). In multivariable models, ILD diagnosis remained associated with MMSE < 24 (odds ratio [OR] 2.72, 95% CI 1.14–6.48), and each 10-percentage-point decrement in DLCO% increased the odds of MMSE < 24 (OR 1.42, 95% CI 1.11–1.92). GAP ≥ 4 was also associated with impaired cognition (OR 2.91, 95% CI 1.13–7.57). Conclusions: Fibrosing ILD, particularly with reduced diffusing capacity and higher GAP stage, is associated with lower MMSE scores and a higher frequency of values below a conventional impairment threshold. Prospective studies incorporating comprehensive neuropsychological testing are needed to determine whether and how neurocognitive assessment should be integrated into routine ILD care. Full article

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by repeated exposure to inhaled antigens in susceptible subjects. High-resolution computed tomography (HRCT) of the lungs is the leading diagnostic method for ILDs, but in some cases HRCT findings are not sufficient to distinguish HP and other ILDs, particularly, fibrotic HP (fHP) and usual interstitial pneumonia (UIP). Objective: The aim of this study was to develop HRCT criteria to diagnose fHP in patients with a UIP-like pattern. Methods: In this retrospective study, we analyzed HRCT scans of patients with fHP and a UIP-like pattern who underwent lung biopsy, and patients with idiopathic pulmonary fibrosis (IPF) and a UIP pattern in HRCT. Results: We included 51 patients with confirmed fHP and 24 patients with IPF/UIP in the analysis. IPF/UIP patients were older, were prevalently males, and did not have any systemic autoimmune diseases or risk factors for other ILDs. fHP patients were younger, with an equal number of males and females, and were more likely to be exposed to environmental antigens. HRCT abnormalities in the fHP group predominated in the lower lung areas or were diffuse in axial scans, whereas IPF/UIP patients mostly demonstrated a diffuse craniocaudal distribution and subpleural axial predominance. Centrilobular nodules and mosaic attenuation were present significantly more often in the fHP group; honeycombing, traction bronchiectasis, and emphysema prevailed in IPF/UIP patients. In the logistic regression analysis, patients with fHP and IPF/UIP differed in the presence of centrilobular nodules, honeycombing, and in both craniocaudal and axial distributions of HRCT abnormalities. In the ROC analysis, the combination of centrilobular nodules, honeycombing, and diffuse axial and craniocaudal distributions can predict the diagnosis of fHP (AUC, 0.953 ± 0.022; 95%CI, 0.910–0.995; p < 0.001). Mosaic attenuation and reticulation did not change the probability of fHP. Conclusions: The most significant HRCT features of fHP compared to the UIP pattern were centrilobular nodules, honeycombing, and a diffuse axial and craniocaudal distribution of abnormal findings. Reticulation, mosaic attenuation, and GGO do not increase the probability of fHP. Full article

Idiopathic pulmonary fibrosis (IPF) is currently defined as a progressive fibrosing interstitial lung disease (ILD) associated with a histopathologic and radiologic pattern of usual interstitial pneumonia (UIP). The relationship between IPF and particles is described, and a pathogenesis for the disease is proposed based on an association with these exposures. In clinical studies and epidemiological investigations, the majority of IPF diagnoses are associated with particle exposures. Cigarette smoking presents the greatest particle challenge in any society, and a relationship with IPF has repeatedly been demonstrated. Environmental exposures to particles other than cigarette smoking, including biomass fuel smoke and ambient air pollution, as well as numerous occupational particle exposures, have also been associated with IPF. The pathogenesis of the disease includes a complexation and sequestration of cell iron at the particle surface, which results in a functional cell deficiency of the requisite metal. In response to the insufficiency of metal in cells, there is the synthesis of biopolymers, including exopolysaccharides (e.g., hyaluronic acid), which accumulate in the extracellular matrix. These biopolymers complex iron and, following depolymerization, facilitate the delivery of the metal intracellularly via receptor-mediated uptake. This process reverses the functional iron deficiency introduced by the particle. Pulmonary fibrosis after particle exposure reflects a response to the modification of a functional intracellular iron deficiency in the lower respiratory tract. The temporal and spatial heterogeneity of IPF results from a dose–response with retained particles and reversibility of the fibrosis. Full article

Progressive pulmonary fibrosis (PPF) is a clinical syndrome associated with worsening quality of life and increased mortality among patients with various interstitial lung diseases. This review aims to update the concepts and criteria that adequately define PPF, aiming to facilitate earlier recognition and optimize clinical management. Fibrosing interstitial lung disease (ILD-f) can progress over time despite optimal management of the underlying conditions. Current criteria for defining PPF include worsening respiratory symptoms, decline in pulmonary function tests (particularly forced vital capacity and diffusing capacity), and radiographic progression over a 1-year follow-up period. However, implementation of these criteria in clinical practice poses challenges. This review discusses the limitations of current evaluation methods and proposes future directions, including the need for validated symptom assessment tools, standardization of pulmonary function testing, and improvements in quantitative radiological evaluation methods. Full article

Objectives: Connective tissue diseases (CTDs) include a diverse group of systemic autoimmune conditions, among which interstitial lung disease (ILD) is acknowledged as a major determinant of prognosis. High-resolution computed tomography (HRCT) is the gold standard for ILD assessment. The distribution of HRCT patterns across CTDs remain incompletely defined. The objective of this systematic review is to synthesize available evidence regarding the prevalence of specific radiological patterns within CTD-ILDs and to assess whether specific patterns occur at different frequencies among individual CTDs. Methods: The inclusion criteria encompassed original human studies published in English between 2015 and 2024, involving adult participants (≥18 years) with CTD-ILDs assessed primarily by HRCT and designed as retrospective, prospective, or cross-sectional trials with extractable data. We systematically searched PubMed, Scopus, and Web of Science (January 2025). Risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS) for cohort and case–control studies, and the JBI Critical Appraisal Checklist for cross-sectional studies. Data were extracted and categorized by HRCT pattern for each CTD, and then summarized descriptively and statistically. Results: We analyzed 23 studies published between 2015 and 2024, which included 2020 patients with CTD-ILDs. The analysis revealed non-specific interstitial pneumonia (NSIP) as the most prevalent pattern overall (36.5%), followed by definite usual interstitial pneumonia (UIP) (24.8%), organizing pneumonia (OP) (9.8%) and lymphoid interstitial pneumonia (LIP) (1.25%). HRCT distribution varied by CTD: NSIP predominated in systemic sclerosis, idiopathic inflammatory myopathies, and mixed connective tissue disease; UIP was most frequent in rheumatoid arthritis; LIP was more common in Sjögren’s syndrome. While global differences were statistically significant, pairwise comparisons often lacked significance, likely due to sample size constraints. Discussion: Limitations include varying risk of bias across study designs, heterogeneity in HRCT reporting, small sample sizes, and inconsistent follow-up, which may reduce precision and generalizability. In addition to the quantitative synthesis, this review offers a detailed description of each radiologic pattern mentioned above, illustrated by representative examples to support the recognition in clinical settings. Furthermore, it includes a brief overview of the major CTDs associated with ILD, summarizing their epidemiological data, risk factors for ILD and clinical presentation and diagnostic recommendations. Conclusions: NSIP emerged as the most common HRCT pattern across CTD-ILDs, with UIP predominating in RA. Although inter-disease differences were observed, statistical significance was limited, likely reflecting sample size constraints. These findings emphasize the diagnostic and prognostic relevance of HRCT pattern recognition and highlight the need for larger, standardized studies. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) registries are established to enhance understanding of its natural history. Methods: Serbia (RS) participated in the EMPIRE (European Multi-Partner IPF Registry) from June 2015 to October 2022, involving four centers. The registry included patients over 18 diagnosed with IPF based on the 2011 international criteria. We aimed to gather key clinical, functional, and survival data, along with treatment information for IPF patients in RS, using a centralized electronic case report for consistency. Results: 188 RS patients participated (median age at diagnosis 65, 63.8% male, 51% smoking history, 56% radiological usual interstitial pneumonia (UIP) pattern). At the diagnosis, median forced vital capacity (FVC) was 73.7% and diffusion capacity for carbon monoxide (DL_CO) was 38%. At initiation of antifibrotic therapy, median FVC was 73.2% (71.5% for deceased, 75.8% for survivors (p = 0.455), and DL_CO was 33.8% (19.9% for deceased, and 35.6% for survivors (p = 0.046)). The median long-term survival from diagnosis was 29.4 months (95% CI: 22.6–36.2 months), and 9.4 months (95% CI: 5.9–12.9 months) from the initiation of therapy, with no difference in the duration of antifibrotic treatment between survivors and deceased (p = 0.598). Conclusions: The RS EMPIRE cohort represents a younger, less comorbid population with fewer smokers and more probable UIP, factors linked to a favorable prognosis. Nevertheless, survival was poorer than expected, mainly due to advanced disease severity at the time of antifibrotic initiation, as indicated by lower DL_CO. These findings highlight the importance of earlier diagnosis and treatment before significant physiological decline to improve outcomes. Full article

Objectives: Accurate differentiation between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) is crucial for guiding treatment in interstitial lung diseases (ILDs). This study evaluates the efficacy of clinical, radiomic, and combined models in classifying UIP and NSIP using high-resolution computed tomography (HRCT) scans. Materials and Methods: A retrospective analysis was performed on 105 HRCT scans (UIP = 60, NSIP = 45) from Faisal Hospital and Research Center. Demographic and pulmonary function data formed the clinical model. Radiomic features, extracted using the pyRadiomics package, were refined using recursive feature elimination. A combined model was developed by integrating clinical and radiomic features to assess their complementary diagnostic value. Model performance was assessed via the area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) analysis, including both global feature importance and individual-level explanations, was used to interpret the model predictions. Results: The clinical model achieved an AUC of 0.62 with a sensitivity of 54% and a specificity of 78%. The radiomic model outperformed it with an AUC of 0.90 with a sensitivity and specificity above 85%. The combined model showed an AUC of 0.86 with a sensitivity of 88% and a specificity of 78%. SHAP analysis identified texture-based features, such as GLCM_Idmn and NGTDM_Contrast, as influential for classification. Conclusions: Radiomic features enhance classification accuracy for UIP and NSIP compared to clinical models. Integrating HCR into clinical workflows may reduce variability and improve diagnostic accuracy in ILD. Future studies should validate findings using larger, multicenter datasets. Full article

Emerging evidence suggests a significant association between monocytes and the pathophysiology and prognosis of idiopathic pulmonary fibrosis (IPF). This review aims to systematically evaluate current knowledge regarding blood monocyte counts and their relationship with the etiology, progression, and prognosis of IPF. We conducted a systematic search in the PubMed database for articles published through 17 February 2025, using the MeSH terms “lung diseases, interstitial” and “monocytes,” which yielded 314 results. After filtering for full-text articles in English (n = 242), we included only studies focusing on blood monocyte counts with clinical implications in IPF. Articles relating to other cell types or non-IPF lung diseases were excluded. Our systematic search identified 12 relevant articles. Monocytes play an essential role in regulating inflammatory responses and resolution across multiple diseases, with established but incompletely understood contributions to lung fibrosis development in IPF. Correlations have been demonstrated between elevated blood monocyte counts and the following: (1) the presence and progression of interstitial lung abnormalities, (2) the progression from an indeterminate usual interstitial pneumonia (UIP) pattern on CT scans to definitive IPF, and (3) worse lung function parameters, an increased risk of acute exacerbations, and reduced overall survival in IPF patients. Monocytes serve as critical orchestrators throughout IPF’s natural history—from early interstitial changes to disease progression and acute exacerbations. Targeting monocyte recruitment pathways and reprogramming their differentiation represents a promising therapeutic approach, while circulating monocyte counts offer potential as accessible biomarkers for disease progression and treatment response. Future research should characterize stage-specific monocyte phenotypes to enable precision-targeted interventions. Full article

Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity of the lungs for carbon monoxide (DLCO) in 26 pSjD patients who presented interstitial changes on the chest CT scan was performed. The titres and positivity rates for anti-SSA/Ro (p = 0.02, p = 0.02) and anti-SSB/La antibodies (p = 0.01, p = 0.001) proved to be significantly increased in patients with abnormal DLCO. Anti-SSB/La antibodies’ titres seemed to be the best predictor for decreased DLCO–AUC 0.791 (0.587–0.994), p = 0.016. A close-to-significance decrease was found in the titres (p = 0.07) and positivity rates—p = 0.09 and OR of 0.15 (0.01–1.63)—of anti-SSB/La antibodies in patients with usual interstitial pneumonia (UIP), indicating their possible protective role against UIP. The lymphocytic interstitial pneumonitis (LIP) pattern on lung CT scan was significantly associated with the simultaneous positivity of the four examined serological markers (p = 0.03). The increase in anti-SSB/La antibody positivity rate in patients with LIP patterns was situated close to the significance level (p = 0.09). Quadruple positivity, as well as isolated anti-SSB/La positivity, could be risk factors for developing LIP in pSjD patients. Thus, anti-SSB/La antibodies might represent a marker of lung involvement in pSjD patients. Full article

Background/Objectives: This study aims to distinguish radiological differences between primary idiopathic Usual Interstitial Pneumonia (UIP) and secondary UIP patterns Methods: This retrospective study included patients with HRCT findings consistent with a UIP pattern. Final diagnoses were established via multidisciplinary discussion and classified as primary UIP/IPF or secondary UIP, following the 2022 ATS/ERS/JRS/ALAT guidelines. An expert thoracic radiologist (>10 years of experience), blinded to clinical data, reviewed the earliest available HRCT assessing key imaging features: honeycombing (micro-, macro- or exuberant), fibrosis distribution (symmetry, anterior-upper lobe sign, etc.), ground-glass opacities (GGO), dilatation of esophagus. Additionally, AI software AVIEW Build 1.1.46.28-win Coreline (©Coreline Soft Co., Ltd. All Rights Reserved). performed lung texture analysis, quantifying total lung volume and radiological patterns. Statistical analysis was performed to reveal results. Results: Among 53 cases, 31 were classified as IPF and 22 as secondary UIP cases. The expert radiologist achieved a diagnostic sensitivity of 82.9%, specificity of 889%, with a positive predictive value of 93.5%—in distinguishing between primary and secondary UIP. Primary UIP cases exhibited typical hallmark radiological features, including uniform honeycombing with cranio-caudal distribution (90.3%). Reticulations contributed significantly to the fibrotic texture, maintaining a consistent cranio-caudal gradient and axial symmetry (84.8%). Secondary UIP displayed more significant radiological heterogeneity, including patchy fibrosis with irregular GGO distribution (84.5% versus 53.33%); other findings—such as exuberant honeycombing, four corner sign and wedge-shaped fibrosis—were mainly observed in secondary pattern with respective percentages of 31.8%, 9% and 49%. Conclusions: Experienced thoracic radiologists, leveraging hallmark imaging features, play a critical role in improving diagnostic accuracy between primary and secondary UIP patterns. Full article

Interstitial lung disease (ILD) is a group of diffuse parenchymal disorders, which are diagnosed in many cases by multidisciplinary discussion (MDD). In some cases, diagnosis can be challenging, and the addition of histopathology can increase diagnostic confidence. The tools to obtain a histopathological sample to diagnose ILD are expanding. In this review, we will discuss the various modalities, their sensitivities and specificities, and procedural complication rates. In this review, we conducted a comprehensive review of literature focusing on emerging and established diagnostic tools for ILD. A systematic search of peer-reviewed publications was performed using PubMed with a focus on clinical trials, retrospective and prospective cohort studies, and systematic reviews. The key diagnostic modalities in focus were genomic classifier (GC), transbronchial cryobiopsy (TBLC), surgical lung biopsy (SLB), endobronchial ultrasound cryobiopsy (EBUS-C), genetic testing, and speckled transthoracic echocardiography (STE). Data extracted from these studies focused on diagnostic yield, specificity, sensitivity, and procedural complication rate. Genomic classifier, a gene-based molecular diagnostic tool, has a high specificity for histological usual interstitial pneumonia (UIP). However, in cases of a negative result, it often results in a need for further invasive sampling by TBLC or SLB. TBLC results in a larger histological sample, which can increase diagnostic yield and increase diagnostic confidence at MDD. Recent prospective trials have compared this modality with SLB and found 63–77% interobserver agreement between pathologists. SLB remains the gold standard with diagnostic yields reported to be more than 90%. EBUS-C has shown promising results increasing diagnostic yield in patients with suspected sarcoidosis or lymphoma. All diagnostic modalities have procedural complications with most common being pneumothorax, bleeding and, rarely, death. Advancements in diagnostic tools for interstitial lung disease (ILD) have significantly improved accuracy. Even though surgical lung biopsy remains the gold standard, the alternative modalities are promising and provide a promising yield with a lower procedural risk. Full article

Interstitial lung diseases (ILD) represent a diverse group of disorders that primarily affect the pulmonary interstitium and, less commonly, involve the alveolar and vascular epithelium. Overlapping clinical, radiological and histopathological features make proper classification difficult, requiring multiple complementary methodologies, including flow cytometry of bronchoalveolar lavages (BAL). This retrospective study analyzed BAL flow cytometry data from 1074 real-life patients, quantifying alveolar macrophages, CD4/CD8 lymphocytes, neutrophils, eosinophils, and CD1a+ Langerhans cells, with the aim of evaluating its diagnostic utility in ILD and pulmonary infection. Clustering and logistic regression analyses identified seven distinct leukocyte profiles: lymphocytic (associated with hypersensitivity pneumonitis, cryptogenic organizing pneumonia, and lymphocytic interstitial pneumonia), sarcoidosis, macrophagic (including nonspecific interstitial pneumonia, desquamative interstitial pneumonitis, pneumoconiosis, and unclassifiable ILD), neutrophilic (including usual interstitial pneumonia, respiratory bronchiolitis ILD, and acute interstitial pneumonia), infectious diseases, eosinophilic ILD, and Langerhans cell histiocytosis. The estimated leukocyte profiles were associated with different overall survival (OS) outcomes. Neutrophilic profiles, both infectious and non-infectious, correlated with poorer OS, particularly in patients without pulmonary fibrosis. Furthermore, corticosteroids and other immunosuppressive therapies did not show significant OS differences across leukocyte profiles. Although the gold standard in BAL cytology continues to be cytopathology, these results support BAL flow cytometry as a rapid and reliable complementary tool to aid in the classification of interstitial lung diseases based on immune cell profiles, providing valuable predictive information and contributing to personalized therapeutic approaches. Full article

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). Methods: This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases “Lazzaro Spallanzani” in Rome, Italy, over three years (2019–2022). Results and Conclusions: Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions. Full article

Usual Interstitial Pneumonia (UIP) is the most severe radiological/histological pattern of Interstitial Lung Disease (ILD). It is typical of Idiopathic Pulmonary Fibrosis (IPF), but is also frequently described in Autoimmune Rheumatic Diseases (ARDs), sharing with IPF common risk factors, genetic backgrounds, and in some cases, disease progression and prognosis. Following the results of the PANTHER study, immunosuppressive drugs are now not recommended for the treatment of IPF; however, their use for the treatment of UIP secondary to ARDs is still under debate. The aim of this review is to summarize existing knowledge on the clinical presentation of autoimmune UIP and its treatment with immunosuppressive drugs. We searched PubMed for English language clinical trials and studies on treatment of ARDs-ILD, looking for specific treatments of UIP-ARDs. The available clinical trials rarely stratify patients by ILD pattern, and clinical studies generally lack a comparison with a placebo group. In Systemic Sclerosis, UIP patients showed a non-significant trend of worsening under immunosuppression. On the contrary, in Interstitial Pneumonia with Autoimmune Features and, above all, Rheumatoid Arthritis, immunosuppressive treatment produced promising results in the management of UIP patients. In conclusion, the current evidence about the immunosuppressive treatment of UIP-ARDs is limited and conflicting. There is an urgent need to adequately assess this topic with specific clinical trials, as has already been performed for IPF. The possibility should be considered that different ARDs can respond differently to immunosuppression. Finally, a wider use of histological samples could produce valuable information from a diagnostic, therapeutic, and research point of view. Full article

Objective: The aim of this study was to determine mortality and predictive factors for death in patients with rheumatoid arthritis (RA) diagnosed with and without interstitial lung disease (ILD). Methods: We retrospectively performed a long-term follow-up study of patients diagnosed with RA at our medical center between April 2001 and June 2023. The diagnosis and classification of ILD were made based on pulmonary high-resolution computed tomography (HRCT), taken at RA diagnosis and during follow-up. Results: Among 781 patients with RA, 78 were diagnosed with ILD; all cases except one were subclinical. The most common HRCT pattern was definite usual interstitial pneumonia (UIP) followed by nonspecific interstitial pneumonia (NSIP)/UIP, probable UIP, NSIP, and early UIP. During follow-up (mean of 10.0 years), the crude incidence rate of death (95% confidence interval [CI]) was 7.1 (5.2–10.0) and 1.5 (1.0–1.9) per 100 person-years in RA patients with and without ILD. Poor control of RA activity was associated with increased incidence rates of death. The standardized mortality ratio (95% CI) compared with the general population was 1.32 (1.11–1.53) for all RA patients, 2.09 (1.45–2.73) for RA-ILD patients, and 1.16 (0.95–1.38) for non-ILD RA patients. Lung cancer and respiratory failure were the most common causes of death in RA-ILD patients. The Multivariable Fine-Gray regression analysis revealed that ILD (adjusted hazard ratio [HR] 2.97 [95% CI 1.95–4.53]), advanced age (1.08 per additional year [1.05–1.10]), and low body mass index (3.07 [2.10–4.49]) were strong predictive factors for mortality in RA patients. HRCT patterns did not affect the risk of death in RA-ILD patients. Conclusions: Regardless of HRCT pattern, RA-ILD contributes to the increased mortality risk in patients with RA. Full article